@article {pmid33860534,
year = {2021},
author = {Yi, Z and Zanolli, C and Liao, W and Wang, W},
title = {A deep-learning-based workflow to assess taxonomic affinity of hominid teeth with a test on discriminating Pongo and Homo upper molars.},
journal = {American journal of physical anthropology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajpa.24286},
pmid = {33860534},
issn = {1096-8644},
support = {40772011//National Natural Science Foundation of China/ ; 41572023//National Natural Science Foundation of China/ ; //Bagui Scholar of Guangxi/ ; },
abstract = {OBJECTIVES: Convolutional neural network (CNN) is a state-of-art deep learning (DL) method with superior performance in image classification. Here, a CNN-based workflow is proposed to discriminate hominid teeth. Our hope is that this method could help confirm otherwise questionable records of Homo from Pleistocene deposits where there is a standing risk of mis-attributing molars of Pongo to Homo.

METHODS AND MATERIALS: A two-step workflow was designed. The first step is converting the enamel-dentine junction (EDJ) into EDJ card, that is, a two-dimensional image conversion of the three-dimensional EDJ surface. In this step, researchers must carefully orient the teeth according to the cervical plane. The second step is training the CNN learner with labeled EDJ cards. A sample consisting of 53 fossil Pongo and 53 Homo (modern human and Neanderthal) was adopted to generate EDJ cards, which were then separated into training set (n = 84) and validation set (n = 22). To assess the feasibility of this workflow, a Pongo-Homo classifier was trained from the aforementioned EDJ card set, and then the classifier was used to predict the taxonomic affinities of six samples (test set) from von Koenigswald's Chinese Apothecary collection.

RESULTS: Results show that EDJ cards in validation set are classified accurately by the CNN learner. More importantly, taxonomic predictions for six specimens in test set match well with the diagnosis results deduced from multiple lines of evidence, implying the great potential of CNN method.

DISCUSSION: This workflow paves a way for future studies using CNN to address taxonomic complexity (e.g., distinguishing Pongo and Homo teeth from the Pleistocene of Asia). Further improvements include visual interpretation and extending the applicability to moderately worn teeth.},
}

@article {pmid33859012,
year = {2021},
author = {Gibbons, A},
title = {DNA from cave dirt traces Neanderthal upheaval.},
journal = {Science (New York, N.Y.)},
volume = {372},
number = {6539},
pages = {222-223},
doi = {10.1126/science.372.6539.222},
pmid = {33859012},
issn = {1095-9203},
}

@article {pmid33858989,
year = {2021},
author = {Vernot, B and Zavala, EI and Gómez-Olivencia, A and Jacobs, Z and Slon, V and Mafessoni, F and Romagné, F and Pearson, A and Petr, M and Sala, N and Pablos, A and Aranburu, A and de Castro, JMB and Carbonell, E and Li, B and Krajcarz, MT and Krivoshapkin, AI and Kolobova, KA and Kozlikin, MB and Shunkov, MV and Derevianko, AP and Viola, B and Grote, S and Essel, E and Herráez, DL and Nagel, S and Nickel, B and Richter, J and Schmidt, A and Peter, B and Kelso, J and Roberts, RG and Arsuaga, JL and Meyer, M},
title = {Unearthing Neanderthal population history using nuclear and mitochondrial DNA from cave sediments.},
journal = {Science (New York, N.Y.)},
volume = {},
number = {},
pages = {},
doi = {10.1126/science.abf1667},
pmid = {33858989},
issn = {1095-9203},
abstract = {Bones and teeth are important sources of Pleistocene hominin DNA, but are rarely recovered at archaeological sites. Mitochondrial DNA has been retrieved from cave sediments, but provides limited value for studying population relationships. We therefore developed methods for the enrichment and analysis of nuclear DNA from sediments, and applied them to cave deposits in western Europe and southern Siberia dated to between approximately 200,000 and 50,000 years ago. We detect a population replacement in northern Spain approximately 100,000 years ago, accompanied by a turnover of mitochondrial DNA. We also identify two radiation events in Neanderthal history during the early part of the Late Pleistocene. Our work lays the ground for studying the population history of ancient hominins from trace amounts of nuclear DNA in sediments.},
}

@article {pmid33854233,
year = {2021},
author = {Choin, J and Mendoza-Revilla, J and Arauna, LR and Cuadros-Espinoza, S and Cassar, O and Larena, M and Ko, AM and Harmant, C and Laurent, R and Verdu, P and Laval, G and Boland, A and Olaso, R and Deleuze, JF and Valentin, F and Ko, YC and Jakobsson, M and Gessain, A and Excoffier, L and Stoneking, M and Patin, E and Quintana-Murci, L},
title = {Genomic insights into population history and biological adaptation in Oceania.},
journal = {Nature},
volume = {},
number = {},
pages = {},
pmid = {33854233},
issn = {1476-4687},
abstract = {The Pacific region is of major importance for addressing questions regarding human dispersals, interactions with archaic hominins and natural selection processes1. However, the demographic and adaptive history of Oceanian populations remains largely uncharacterized. Here we report high-coverage genomes of 317 individuals from 20 populations from the Pacific region. We find that the ancestors of Papuan-related ('Near Oceanian') groups underwent a strong bottleneck before the settlement of the region, and separated around 20,000-40,000 years ago. We infer that the East Asian ancestors of Pacific populations may have diverged from Taiwanese Indigenous peoples before the Neolithic expansion, which is thought to have started from Taiwan around 5,000 years ago2-4. Additionally, this dispersal was not followed by an immediate, single admixture event with Near Oceanian populations, but involved recurrent episodes of genetic interactions. Our analyses reveal marked differences in the proportion and nature of Denisovan heritage among Pacific groups, suggesting that independent interbreeding with highly structured archaic populations occurred. Furthermore, whereas introgression of Neanderthal genetic information facilitated the adaptation of modern humans related to multiple phenotypes (for example, metabolism, pigmentation and neuronal development), Denisovan introgression was primarily beneficial for immune-related functions. Finally, we report evidence of selective sweeps and polygenic adaptation associated with pathogen exposure and lipid metabolism in the Pacific region, increasing our understanding of the mechanisms of biological adaptation to island environments.},
}

@article {pmid33850254,
year = {2021},
author = {Vaesen, K and Dusseldorp, GL and Brandt, MJ},
title = {Author Correction: An emerging consensus in palaeoanthropology: demography was the main factor responsible for the disappearance of Neanderthals.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {8450},
doi = {10.1038/s41598-021-88189-5},
pmid = {33850254},
issn = {2045-2322},
}

@article {pmid33833103,
year = {2021},
author = {Gibbons, A},
title = {When modern humans met Neanderthals.},
journal = {Science (New York, N.Y.)},
volume = {372},
number = {6538},
pages = {115-116},
doi = {10.1126/science.372.6538.115},
pmid = {33833103},
issn = {1095-9203},
}

@article {pmid33828320,
year = {2021},
author = {Hajdinjak, M and Mafessoni, F and Skov, L and Vernot, B and Hübner, A and Fu, Q and Essel, E and Nagel, S and Nickel, B and Richter, J and Moldovan, OT and Constantin, S and Endarova, E and Zahariev, N and Spasov, R and Welker, F and Smith, GM and Sinet-Mathiot, V and Paskulin, L and Fewlass, H and Talamo, S and Rezek, Z and Sirakova, S and Sirakov, N and McPherron, SP and Tsanova, T and Hublin, JJ and Peter, BM and Meyer, M and Skoglund, P and Kelso, J and Pääbo, S},
title = {Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry.},
journal = {Nature},
volume = {592},
number = {7853},
pages = {253-257},
pmid = {33828320},
issn = {1476-4687},
abstract = {Modern humans appeared in Europe by at least 45,000 years ago1-5, but the extent of their interactions with Neanderthals, who disappeared by about 40,000 years ago6, and their relationship to the broader expansion of modern humans outside Africa are poorly understood. Here we present genome-wide data from three individuals dated to between 45,930 and 42,580 years ago from Bacho Kiro Cave, Bulgaria1,2. They are the earliest Late Pleistocene modern humans known to have been recovered in Europe so far, and were found in association with an Initial Upper Palaeolithic artefact assemblage. Unlike two previously studied individuals of similar ages from Romania7 and Siberia8 who did not contribute detectably to later populations, these individuals are more closely related to present-day and ancient populations in East Asia and the Americas than to later west Eurasian populations. This indicates that they belonged to a modern human migration into Europe that was not previously known from the genetic record, and provides evidence that there was at least some continuity between the earliest modern humans in Europe and later people in Eurasia. Moreover, we find that all three individuals had Neanderthal ancestors a few generations back in their family history, confirming that the first European modern humans mixed with Neanderthals and suggesting that such mixing could have been common.},
}

@article {pmid33828282,
year = {2021},
author = {Callaway, E},
title = {Oldest DNA from a Homo sapiens reveals surprisingly recent Neanderthal ancestry.},
journal = {Nature},
volume = {592},
number = {7854},
pages = {339},
pmid = {33828282},
issn = {1476-4687},
}

@article {pmid33828250,
year = {2021},
author = {Lalueza-Fox, C},
title = {Neanderthal assimilation?.},
journal = {Nature ecology & evolution},
volume = {},
number = {},
pages = {},
pmid = {33828250},
issn = {2397-334X},
}

@article {pmid33828249,
year = {2021},
author = {Prüfer, K and Posth, C and Yu, H and Stoessel, A and Spyrou, MA and Deviese, T and Mattonai, M and Ribechini, E and Higham, T and Velemínský, P and Brůžek, J and Krause, J},
title = {A genome sequence from a modern human skull over 45,000 years old from Zlatý kůň in Czechia.},
journal = {Nature ecology & evolution},
volume = {},
number = {},
pages = {},
pmid = {33828249},
issn = {2397-334X},
support = {324139//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; 324139//EC | EU Framework Programme for Research and Innovation H2020 | H2020 European Institute of Innovation and Technology (H2020 The European Institute of Innovation and Technology)/ ; DKRVO 2019-2023/7.I.c, 00023272//Ministerstvo Kultury (Ministry of Culture, Czech Republic)/ ; },
abstract = {Modern humans expanded into Eurasia more than 40,000 years ago following their dispersal out of Africa. These Eurasians carried ~2-3% Neanderthal ancestry in their genomes, originating from admixture with Neanderthals that took place sometime between 50,000 and 60,000 years ago, probably in the Middle East. In Europe, the modern human expansion preceded the disappearance of Neanderthals from the fossil record by 3,000-5,000 years. The genetic makeup of the first Europeans who colonized the continent more than 40,000 years ago remains poorly understood since few specimens have been studied. Here, we analyse a genome generated from the skull of a female individual from Zlatý kůň, Czechia. We found that she belonged to a population that appears to have contributed genetically neither to later Europeans nor to Asians. Her genome carries ~3% Neanderthal ancestry, similar to those of other Upper Palaeolithic hunter-gatherers. However, the lengths of the Neanderthal segments are longer than those observed in the currently oldest modern human genome of the ~45,000-year-old Ust'-Ishim individual from Siberia, suggesting that this individual from Zlatý kůň is one of the earliest Eurasian inhabitants following the expansion out of Africa.},
}

@article {pmid33798098,
year = {2021},
author = {Devièse, T and Abrams, G and Hajdinjak, M and Pirson, S and De Groote, I and Di Modica, K and Toussaint, M and Fischer, V and Comeskey, D and Spindler, L and Meyer, M and Semal, P and Higham, T},
title = {Reevaluating the timing of Neanderthal disappearance in Northwest Europe.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {118},
number = {12},
pages = {},
pmid = {33798098},
issn = {1091-6490},
abstract = {Elucidating when Neanderthal populations disappeared from Eurasia is a key question in paleoanthropology, and Belgium is one of the key regions for studying the Middle to Upper Paleolithic transition. Previous radiocarbon dating placed the Spy Neanderthals among the latest surviving Neanderthals in Northwest Europe with reported dates as young as 23,880 ± 240 B.P. (OxA-8912). Questions were raised, however, regarding the reliability of these dates. Soil contamination and carbon-based conservation products are known to cause problems during the radiocarbon dating of bulk collagen samples. Employing a compound-specific approach that is today the most efficient in removing contamination and ancient genomic analysis, we demonstrate here that previous dates produced on Neanderthal specimens from Spy were inaccurately young by up to 10,000 y due to the presence of unremoved contamination. Our compound-specific radiocarbon dates on the Neanderthals from Spy and those from Engis and Fonds-de-Forêt demonstrate that they disappeared from Northwest Europe at 44,200 to 40,600 cal B.P. (at 95.4% probability), much earlier than previously suggested. Our data contribute significantly to refining models for Neanderthal disappearance in Europe and, more broadly, show that chronometric models regarding the appearance or disappearance of animal or hominin groups should be based only on radiocarbon dates obtained using robust pretreatment methods.},
}

@article {pmid33797824,
year = {2021},
author = {Ocobock, C and Lacy, S and Niclou, A},
title = {Between a rock and a cold place: Neanderthal biocultural cold adaptations.},
journal = {Evolutionary anthropology},
volume = {},
number = {},
pages = {},
doi = {10.1002/evan.21894},
pmid = {33797824},
issn = {1520-6505},
abstract = {A large body of work focuses on the unique aspects of Neanderthal anatomy, inferred physiology, and behavior to test the assumption that Neanderthals were hyper-adapted to living in cold environments. This research has expanded over the years to include previously unexplored and potentially adaptive features such as brown adipose tissue and fire-usage. Here we review the current state of knowledge of Neanderthal cold adaptations along morphological, physiological, and behavioral lines. While highlighting foundational as well as recent work, we also emphasize key areas for future research. Despite thriving in a variety of climates, it is well-accepted that Neanderthals appear to be the most cold-adapted of known fossil hominin groups; however, there are still many unknowns. There is a great deal yet to be uncovered about the nature and manifestation of Neanderthal adaptation and how the synergy of biology and culture helped buffer them against extreme and variable environments.},
}

@article {pmid33794419,
year = {2021},
author = {Baab, KL and Nesbitt, A and Hublin, JJ and Neubauer, S},
title = {Assessing the status of the KNM-ER 42700 fossil using Homo erectus neurocranial development.},
journal = {Journal of human evolution},
volume = {154},
number = {},
pages = {102980},
doi = {10.1016/j.jhevol.2021.102980},
pmid = {33794419},
issn = {1095-8606},
abstract = {Based on ontogenetic data of endocranial shape, it has been proposed that a younger than previously assumed developmental status of the 1.5-Myr-old KNM-ER 42700 calvaria could explain why the calvaria of this fossil does not conform to the shape of other Homo erectus individuals. Here, we investigate (ecto)neurocranial ontogeny in H. erectus and assess the proposed juvenile status of this fossil using recent Homo sapiens, chimpanzees (Pan troglodytes), and Neanderthals (Homo neanderthalensis) to model and discuss changes in neurocranial shape from the juvenile to adult stages. We show that all four species share common patterns of developmental shape change resulting in a relatively lower cranial vault and expanded supraorbital torus at later developmental stages. This finding suggests that ectoneurocranial data from extant hominids can be used to model the ontogenetic trajectory for H. erectus, for which only one well-preserved very young individual is known. However, our study also reveals differences in the magnitudes and, to a lesser extent, directions of the species-specific trajectories that add to the overall shared pattern of neurocranial shape changes. We demonstrate that the very young H. erectus juvenile from Mojokerto together with subadult and adult H. erectus individuals cannot be accommodated within the pattern of the postnatal neurocranial trajectory for humans. Instead, the chimpanzee pattern might be a better 'fit' for H. erectus despite their more distant phylogenetic relatedness. The data are also compatible with an ontogenetic shape trajectory that is in some regards intermediate between that of recent H. sapiens and chimpanzees, implying a unique trajectory for H. erectus that combines elements of both extant species. Based on this new knowledge, neurocranial shape supports the assessment that KNM-ER 42700 is a young juvenile H. erectus if H. erectus followed an ontogenetic shape trajectory that was more similar to chimpanzees than humans.},
}

@article {pmid33791713,
year = {2021},
author = {Huffman, J and Butler-Laporte, G and Khan, A and Drivas, TG and Peloso, GM and Nakanishi, T and Verma, A and Kiryluk, K and Richards, JB and Zeberg, H},
title = {Alternative splicing of OAS1 alters the risk for severe COVID-19.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {33791713},
support = {UL1 TR001873/TR/NCATS NIH HHS/United States ; UL1 TR001878/TR/NCATS NIH HHS/United States ; },
abstract = {A locus containing OAS1/2/3 has been identified as a risk locus for severe COVID-19 among Europeans ancestry individuals, with a protective haplotype of ∼75 kilobases derived from Neanderthals. Here, we show that among several potentially causal variants at this locus, a splice variant of OAS1 occurs in people of African ancestry independently of the Neanderthal haplotype and confers protection against COVID-19 of a magnitude similar to that seen in individuals without African ancestry.},
}

@article {pmid33787889,
year = {2021},
author = {Yair, S and Lee, KM and Coop, G},
title = {The timing of human adaptation from Neanderthal introgression.},
journal = {Genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/genetics/iyab052},
pmid = {33787889},
issn = {1943-2631},
abstract = {Admixture has the potential to facilitate adaptation by providing alleles that are immediately adaptive in a new environment or by simply increasing the long term reservoir of genetic diversity for future adaptation. A growing number of cases of adaptive introgression are being identified in species across the tree of life, however the timing of selection, and therefore the importance of the different evolutionary roles of admixture, is typically unknown. Here, we investigate the spatio-temporal history of selection favoring Neanderthal-introgressed alleles in modern human populations. Using both ancient and present-day samples of modern humans, we integrate the known demographic history of populations, namely population divergence and migration, with tests for selection. We model how a sweep placed along different branches of an admixture graph acts to modify the variance and covariance in neutral allele frequencies among populations at linked loci. Using a method based on this model of allele frequencies, we study previously identified cases of Neanderthal adaptive introgression. From these, we identify cases in which Neanderthal introgressed alleles were quickly beneficial and other cases in which they persisted at low frequency for some time. For some of the alleles that persisted at low frequency, we show that selection likely independently favored them later on in geographically separated populations. Our work highlights how admixture with ancient hominins has contributed to modern human adaptation and contextualizes observed levels of Neanderthal ancestry in present-day and ancient samples.},
}

@article {pmid33774376,
year = {2021},
author = {Chevalier, T and Colard, T and Colombo, A and Golovanova, L and Doronichev, V and Hublin, JJ},
title = {Early ontogeny of humeral trabecular bone in Neandertals and recent modern humans.},
journal = {Journal of human evolution},
volume = {154},
number = {},
pages = {102968},
doi = {10.1016/j.jhevol.2021.102968},
pmid = {33774376},
issn = {1095-8606},
abstract = {Trabecular bone ontogeny is well known in modern humans and unknown in Neandertals. Yet the bone developmental pattern is useful for interpreting fossils from evolutionary and functional perspectives. Interestingly, microstructure in early ontogeny is supposedly not influenced by high and specific mechanical loading related to the lifestyle of a human group and consequently does not directly depend on the activities of hunter-gatherers. Here, we specifically explored the early growth trajectories of the trabecular bone structure of the humerus and emphasized in particular how bone fraction (bone volume/total volume [BV/TV]) was built up in Neandertals, given the specific modern human bone loss after birth and the use of BV/TV in functional studies. Six Neandertals and 26 recent modern humans ranging from perinates to adolescents were included in this study. Six trabecular parameters were measured within a cubic region of interest extracted from the proximal metaphysis of the humerus. We found that the microstructural changes in Neandertals during early ontogeny (<1 year) fit with modern human growth trajectories for each parameter. The specific bone loss occurring immediately after birth in modern humans also occurred in Neandertals (but not in chimpanzees). However, the early childhood fossil Ferrassie 6 presented unexpectedly high BV/TV, whereas the high BV/TV in the Crouzade I adolescent was predictable. These results suggest that Neandertals and modern humans shared predetermined early growth trajectories and developmental mechanisms. We assume that the close relationship between skeletal characteristics in early ontogeny and adults in modern humans also existed in Neandertals. However, it was difficult to ensure that the high BV/TV in Neandertal early childhood, represented by only one individual, was at the origin of the high BV/TV observed in adults. Consequently, our study does not challenge the mechanical hypothesis that explains the trabecular gracilization of the humerus during the Holocene.},
}

@article {pmid33707474,
year = {2021},
author = {Mayoral, E and Díaz-Martínez, I and Duveau, J and Santos, A and Ramírez, AR and Morales, JA and Morales, LA and Díaz-Delgado, R},
title = {Tracking late Pleistocene Neandertals on the Iberian coast.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {4103},
pmid = {33707474},
issn = {2045-2322},
support = {PID2019-104625RB-100//Ministry of Science and Innovation of Spain/ ; RNM276//Andalusian Government to the Research Group/ ; EJ IT1418-19.//Basque Government to the Research Group/ ; },
abstract = {Here, we report the recent discovery of 87 Neandertal footprints on the Southwest of the Iberian Peninsula (Doñana shoreline, Spain) located on an upper Pleistocene aeolian littoral setting (about 106 ± 19 kyr). Morphometric comparisons, high resolution digital photogrammetric 3D models and detailed sedimentary analysis have been provided to characterized the footprints and the palaeoenvironment. The footprints were impressed in the shoreline of a hypersaline swamped area related to benthic microbial mats, close to the coastline. They have a rounded heel, a longitudinal arch, relatively short toes, and adducted hallux, and represent the oldest upper Pleistocene record of Neandertal footprints in the world. Among these 87 footprints, 31 are longitudinally complete and measure from 14 to 29 cm. The calculated statures range from 104 to 188 cm, with half of the data between 130 and 150 cm. The wide range of sizes of the footprints suggests the existence of a social group integrated by individuals of different age classes but dominated, however, by non-adult individuals. The footprints, which are outside the flooded area are oriented perpendicular to the shoreline. These 87 footprints reinforce the ecological scenario of Neandertal groups established in coastal areas.},
}

@article {pmid33707343,
year = {2021},
author = {García-Campos, C and Martinén-Torres, M and Modesto-Mata, M and Martín-Francés, L and Martínez de Pinillos, M and Bermúdez de Castro, JM},
title = {Indicators of sexual dimorphism in Homo antecessor permanent canines.},
journal = {Journal of anthropological sciences = Rivista di antropologia : JASS},
volume = {99},
number = {},
pages = {},
doi = {10.4436/JASS.99001},
pmid = {33707343},
issn = {2037-0644},
abstract = {One of the main concerns of paleoanthropologists is to make a correct interpretation of the variability observed in the fossil record. However, the current knowledge about sexual dimorphism in the human lineage comes mainly from the study of modern human, Neanderthal and pre-Neanderthal populations, whereas information available about the intrapopulation variability of the groups that preceded these taxa is still ambiguous. In this preliminary study, Homo antecessor dental sample was assessed with the aim of trying to evaluate the degree of variability of their permanent canines` dental tissue proportions. Microtomographic techniques were here employed in order to measure and compare the crown volumes and surface areas of their enamel caps and dentine-pulp complexes. Then, the Pearson`s Coefficient of Variation and the Euclidean Distance were assessed to evaluate of intrapopulation variability of Gran Dolina TD6.2 dental sample. The values obtained were also compared with those of the dental samples from Sima de los Huesos site (Spain), the Neanderthal site of Krapina (Croatia), as well as from a broad forensic collection of known sex. Our results showed a marked intrapopulation variability in the dental tissues measurements of the canines of the individuals H1 and H3 from this site. This variability may be interpreted as an indicator of sexual dimorphism. If this is the case, H1 may be considered as a male individual, whereas H3 would be a female. Future discoveries of new fossils in the level TD6.2 of Gran Dolina site might help to confirm or refute this hypothesis.},
}

@article {pmid33674720,
year = {2021},
author = {Banks, WE and Moncel, MH and Raynal, JP and Cobos, ME and Romero-Alvarez, D and Woillez, MN and Faivre, JP and Gravina, B and d'Errico, F and Locht, JL and Santos, F},
title = {An ecological niche shift for Neanderthal populations in Western Europe 70,000 years ago.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {5346},
pmid = {33674720},
issn = {2045-2322},
support = {ANR-10-LABX-52//Agence Nationale de la Recherche/ ; ANR-19-CE27-0011-03//Agence Nationale de la Recherche/ ; 2010-159, 2011-61, 2014-142//Ministère de la Culture et de la Communication/ ; FP7/2007-2013: 249587/ERC_/European Research Council/International ; PIA IdEx//Université de Bordeaux/ ; SapienCE project 262618//Research Council of Norway/ ; },
abstract = {Middle Paleolithic Neanderthal populations occupied Eurasia for at least 250,000 years prior to the arrival of anatomically modern humans. While a considerable body of archaeological research has focused on Neanderthal material culture and subsistence strategies, little attention has been paid to the relationship between regionally specific cultural trajectories and their associated existing fundamental ecological niches, nor to how the latter varied across periods of climatic variability. We examine the Middle Paleolithic archaeological record of a naturally constrained region of Western Europe between 82,000 and 60,000 years ago using ecological niche modeling methods. Evaluations of ecological niche estimations, in both geographic and environmental dimensions, indicate that 70,000 years ago the range of suitable habitats exploited by these Neanderthal populations contracted and shifted. These ecological niche dynamics are the result of groups continuing to occupy habitual territories that were characterized by new environmental conditions during Marine Isotope Stage 4. The development of original cultural adaptations permitted this territorial stability.},
}

@article {pmid33649543,
year = {2021},
author = {Conde-Valverde, M and Martínez, I and Quam, RM and Rosa, M and Velez, AD and Lorenzo, C and Jarabo, P and Bermúdez de Castro, JM and Carbonell, E and Arsuaga, JL},
title = {Neanderthals and Homo sapiens had similar auditory and speech capacities.},
journal = {Nature ecology & evolution},
volume = {},
number = {},
pages = {},
pmid = {33649543},
issn = {2397-334X},
abstract = {The study of audition in fossil hominins is of great interest given its relationship with intraspecific vocal communication. While the auditory capacities have been studied in early hominins and in the Middle Pleistocene Sima de los Huesos hominins, less is known about the hearing abilities of the Neanderthals. Here, we provide a detailed approach to their auditory capacities. Relying on computerized tomography scans and a comprehensive model from the field of auditory bioengineering, we have established sound power transmission through the outer and middle ear and calculated the occupied bandwidth in Neanderthals. The occupied bandwidth is directly related to the efficiency of the vocal communication system of a species. Our results show that the occupied bandwidth of Neanderthals was greater than the Sima de los Huesos hominins and similar to extant humans, implying that Neanderthals evolved the auditory capacities to support a vocal communication system as efficient as modern human speech.},
}

@article {pmid33649483,
year = {2021},
author = {Vaesen, K and Dusseldorp, GL and Brandt, MJ},
title = {An emerging consensus in palaeoanthropology: demography was the main factor responsible for the disappearance of Neanderthals.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {4925},
pmid = {33649483},
issn = {2045-2322},
abstract = {The causes of Neanderthal disappearance about 40,000 years ago remain highly contested. Over a dozen serious hypotheses are currently endorsed to explain this enigmatic event. Given the relatively large number of contending explanations and the relatively large number of participants in the debate, it is unclear how strongly each contender is supported by the research community. What does the community actually believe about the demise of Neanderthals? To address this question, we conducted a survey among practicing palaeo-anthropologists (total number of respondents = 216). It appears that received wisdom is that demography was the principal cause of the demise of Neanderthals. In contrast, there is no received wisdom about the role that environmental factors and competition with modern humans played in the extinction process; the research community is deeply divided about these issues. Finally, we tested the hypothesis that palaeo-anthropologists' stand in the debate co-varies with their socio-political views and attitudes. We found no evidence for such a correlation.},
}

@article {pmid33644865,
year = {2021},
author = {Richards, GD and Guipert, G and Jabbour, RS and Defleur, AR},
title = {Neanderthal cranial remains from Baume Moula-Guercy (Soyons, Ardèche, France).},
journal = {American journal of physical anthropology},
volume = {175},
number = {1},
pages = {201-226},
doi = {10.1002/ajpa.24256},
pmid = {33644865},
issn = {1096-8644},
support = {//Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA/ ; },
abstract = {OBJECTIVES: We provide the first comparative description of the Guercy 1 cranium and isolated cranial fragments from Baume Moula-Guercy and examine their affinities to European Preneanderthals, Neanderthals, and Homo sapiens.

MATERIALS AND METHODS: The Moula-Guercy hominins derive from deposits chronostratigraphically and biostratigraphically dated to the Eemian Interglacial (MIS 5e). For comparisons we compiled a sample of European and Southwest Asian subadult-adult Middle-to-Late Pleistocene hominins (≈MIS 14-MIS 2; N = 184). This sample represents a Preneanderthal-Neanderthal group and a H. sapiens group, both of which were further divided into three time-successive subgroups defined by associated marine isotope stages (MIS). Metric and morphological observations were made on the original fossils and a virtual reconstruction of Guercy 1. Developmental age and sex and the minimum-maximum number of individuals were assessed.

RESULTS: Guercy 1 represents the remains of a late stage adolescent (≈15-16.0 years) female. Morphological and metric data combine to associate the total morphological pattern expressed in Guercy 1 with our MIS 7-MIS 5e ("Early Neanderthal") subgroup. Some features, especially those related to the frontal, suggest linkage to a paleodeme comprising the Moula-Guercy, Artenac, La Chaise Abri Suard and, possibly, the Biache-Saint-Vaast samples.

DISCUSSION: Remains of MIS 7-MIS 5e Neanderthals are rare and fragmentary, especially those dated to the Last Interglacial. The Baume Moula-Guercy sample provides new insights into the total morphological pattern expressed in MIS 5e Neanderthals. Further, our results support earlier suggestions that MIS 7-MIS 5e European hominins represent a morphotype that is distinct from both earlier and later members of the Preneanderthal-Neanderthal group.},
}

@article {pmid33638923,
year = {2021},
author = {Mora-Bermúdez, F and Taverna, E and Huttner, WB},
title = {From stem and progenitor cells to neurons in the developing neocortex: key differences among hominids.},
journal = {The FEBS journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/febs.15793},
pmid = {33638923},
issn = {1742-4658},
abstract = {Comparing the biology of humans to that of other primates, and notably other hominids, is a useful path to learn more about what makes us human. Some of the most interesting differences among hominids are closely related to brain development and function, for example behaviour and cognition. This makes it particularly interesting to compare the hominid neural cells of the neocortex, a part of the brain that plays central roles in those processes. However, well-preserved tissue from great apes is usually extremely difficult to obtain. A variety of new alternative tools, for example brain organoids, are now beginning to make it possible to search for such differences and analyse their potential biological and biomedical meaning. Here, we present an overview of recent findings from comparisons of the neural stem and progenitor cells (NSPCs) and neurons of hominids. In addition to differences in proliferation and differentiation of NSPCs, and maturation of neurons, we highlight that the regulation of the timing of these processes is emerging as a general foundational difference in the development of the neocortex of hominids.},
}

@article {pmid33633408,
year = {2021},
author = {Zhou, S and Butler-Laporte, G and Nakanishi, T and Morrison, DR and Afilalo, J and Afilalo, M and Laurent, L and Pietzner, M and Kerrison, N and Zhao, K and Brunet-Ratnasingham, E and Henry, D and Kimchi, N and Afrasiabi, Z and Rezk, N and Bouab, M and Petitjean, L and Guzman, C and Xue, X and Tselios, C and Vulesevic, B and Adeleye, O and Abdullah, T and Almamlouk, N and Chen, Y and Chassé, M and Durand, M and Paterson, C and Normark, J and Frithiof, R and Lipcsey, M and Hultström, M and Greenwood, CMT and Zeberg, H and Langenberg, C and Thysell, E and Pollak, M and Mooser, V and Forgetta, V and Kaufmann, DE and Richards, JB},
title = {A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {33633408},
issn = {1546-170X},
abstract = {To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (odds ratio (OR) = 0.54, P = 7 × 10-8), hospitalization (OR = 0.61, P = 8 × 10-8) and susceptibility (OR = 0.78, P = 8 × 10-6). Measuring OAS1 levels in 504 individuals, we found that higher plasma OAS1 levels in a non-infectious state were associated with reduced COVID-19 susceptibility and severity. Further analyses suggested that a Neanderthal isoform of OAS1 in individuals of European ancestry affords this protection. Thus, evidence from MR and a case-control study support a protective role for OAS1 in COVID-19 adverse outcomes. Available pharmacological agents that increase OAS1 levels could be prioritized for drug development.},
}

@article {pmid33620372,
year = {2021},
author = {Baldoni, M and Al-Hashmi, M and Bianchi, AE and Sakal, F and Al-Naimi, F and Leisten, T and Martínez-Labarga, C and Tomei, S},
title = {Bioarchaeology-related studies in the Arabian Gulf: potentialities and shortcomings.},
journal = {Homo : internationale Zeitschrift fur die vergleichende Forschung am Menschen},
volume = {72},
number = {1},
pages = {17-32},
doi = {10.1127/homo/2021/1282},
pmid = {33620372},
issn = {1618-1301},
abstract = {Archaeological studies provide a powerful tool to understand the prehistoric societies, especially when combined to cutting-edge morphological and molecular anthropological analyses, allowing reconstructing past population dynamics, admixture events, and socio-cultural changes. Despite the advances achieved in the last decades by archaeological studies worldwide, several regions of the World have been spared from this scientific improvement due to various reasons. The Arabian Gulf represents a unique ground to investigate, being the passageway for human migrations and one of the hypothesized areas in which Neanderthal introgression occurred. A number of archaeological sites are currently present in the Arabian Gulf and have witnessed the antiquity and the intensiveness of the human settlements in the region. Nevertheless, the archaeological and anthropological investigation in the Gulf is still in its infancy. Data collected through archaeological studies in the area have the potential to help answering adamant questions of human history from the beginning of the structuring of genetic diversity in human species to the Neolithisation process. This review aims at providing an overview of the archaeological studies in the Arabian Gulf with special focus to Qatar, highlighting potentialities and shortcomings.},
}

@article {pmid33619340,
year = {2021},
author = {Zilio, L and Hammond, H and Karampaglidis, T and Sánchez-Romero, L and Blasco, R and Rivals, F and Rufà, A and Picin, A and Chacón, MG and Demuro, M and Arnold, LJ and Rosell, J},
title = {Examining Neanderthal and carnivore occupations of Teixoneres Cave (Moià, Barcelona, Spain) using archaeostratigraphic and intra-site spatial analysis.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {4339},
pmid = {33619340},
issn = {2045-2322},
abstract = {Teixoneres Cave (Moià, Barcelona, Spain) is a reference site for Middle Palaeolithic studies of the Iberian Peninsula. The cave preserves an extensive stratigraphic sequence made up of eight units, which is presented in depth in this work. The main goal of this study is to undertake an initial spatial examination of Unit III, formed during Marine Isotope Stage 3, with the aim of understanding spatial organization and past activities developed by Neanderthals and carnivores (bears, hyenas and smaller carnivores). The total sample analysed includes 38,244 archaeological items and 5888 limestone blocks. The application of GIS tools allows us to clearly distinguish three geologically-defined stratigraphic subunits. Unit III has been previously interpreted as a palimpsest resulting from alternating occupation of the cave by human groups and carnivores. The distribution study shows that faunal specimens, lithic artefacts, hearths and charcoal fragments are significantly concentrated at the entrance of the cave where, it is inferred, hominins carried out different activities, while carnivores preferred the sheltered zones in the inner areas of the cave. The results obtained reveal a spatial pattern characterized by fire use related zones, and show that the site was occupied by Neanderthals in a similar and consistent way throughout the ˃ 7000 years range covered by the analysed subunits. This spatial pattern is interpreted as resulting from repeated short-term human occupations.},
}

@article {pmid33616898,
year = {2021},
author = {González-Urquijo, J and Bailey, SE and Lazuen, T},
title = {Axlor's level IV human remains are convincingly Neanderthals: A reply to Gómez-Olivencia et al.},
journal = {American journal of physical anthropology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajpa.24252},
pmid = {33616898},
issn = {1096-8644},
support = {PID2019-107260GB-I00//Ministerio de Ciencia e Innovación, Spain/ ; },
}

@article {pmid33595856,
year = {2021},
author = {Lee, JW and Lee, IH and Sato, T and Kong, SW and Iimura, T},
title = {Genetic variation analyses indicate conserved SARS-CoV-2-host interaction and varied genetic adaptation in immune response factors in modern human evolution.},
journal = {Development, growth & differentiation},
volume = {},
number = {},
pages = {},
pmid = {33595856},
issn = {1440-169X},
support = {U01 TR002623/TR/NCATS NIH HHS/United States ; R24OD024622//National Institution of Health/ ; R01MH107205//National Institution of Health/ ; R01 MH107205/MH/NIMH NIH HHS/United States ; 18H02983//Grant-in-Aids for Scientific Research from the Japan Society for the Promotion of Science (JSPS KAKENHI)/ ; PK43200005//Takeda Science Foundation/ ; 18K19649//Grant-in-Aids for Scientific Research from the Japan Society for the Promotion of Science (JSPS KAKENHI)/ ; U01TR002623//National Institution of Health/ ; 19K10044//Grant-in-Aids for Scientific Research from the Japan Society for the Promotion of Science (JSPS KAKENHI)/ ; R24 OD024622/OD/NIH HHS/United States ; },
abstract = {Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pandemic as of early 2020. Upon infection, SARS-CoV-2 attaches to its receptor, that is, angiotensin-converting enzyme 2 (ACE2), on the surface of host cells and is then internalized into host cells via enzymatic machineries. This subsequently stimulates immune response factors. Since the host immune response and severity of COVID-19 vary among individuals, genetic risk factors for severe COVID-19 cases have been investigated. Our research group recently conducted a survey of genetic variants among SARS-CoV-2-interacting molecules across populations, noting near absence of difference in allele frequency spectrum between populations in these genes. Recent genome-wide association studies have identified genetic risk factors for severe COVID-19 cases in a segment of chromosome 3 that involves six genes encoding three immune-regulatory chemokine receptors and another three molecules. The risk haplotype seemed to be inherited from Neanderthals, suggesting genetic adaptation against pathogens in modern human evolution. Therefore, SARS-CoV-2 uses highly conserved molecules as its virion interaction, whereas its immune response appears to be genetically biased in individuals to some extent. We herein review the molecular process of SARS-CoV-2 infection as well as our further survey of genetic variants of its related immune effectors. We also discuss aspects of modern human evolution.},
}

@article {pmid33593941,
year = {2021},
author = {Zeberg, H and Pääbo, S},
title = {A genomic region associated with protection against severe COVID-19 is inherited from Neandertals.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {118},
number = {9},
pages = {},
pmid = {33593941},
issn = {1091-6490},
mesh = {Animals ; COVID-19/*genetics/immunology ; Chromosomes, Human, Pair 12/*genetics ; *Evolution, Molecular ; *Genetic Predisposition to Disease ; Haplotypes ; Humans ; Neanderthals/*genetics ; Quantitative Trait Loci ; },
abstract = {It was recently shown that the major genetic risk factor associated with becoming severely ill with COVID-19 when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is inherited from Neandertals. New, larger genetic association studies now allow additional genetic risk factors to be discovered. Using data from the Genetics of Mortality in Critical Care (GenOMICC) consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease. It also differs from the risk haplotype in that it has a more moderate effect and occurs at substantial frequencies in all regions of the world outside Africa. Among ancient human genomes in western Eurasia, the frequency of the protective Neandertal haplotype may have increased between 20,000 and 10,000 y ago and again during the past 1,000 y.},
}

Animals
COVID-19/*genetics/immunology
Chromosomes, Human, Pair 12/*genetics
*Evolution, Molecular
*Genetic Predisposition to Disease
Haplotypes
Humans
Neanderthals/*genetics
Quantitative Trait Loci

@article {pmid33589653,
year = {2021},
author = {Blinkhorn, J and Zanolli, C and Compton, T and Groucutt, HS and Scerri, EML and Crété, L and Stringer, C and Petraglia, MD and Blockley, S},
title = {Nubian Levallois technology associated with southernmost Neanderthals.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {2869},
pmid = {33589653},
issn = {2045-2322},
support = {RPG-2017-087//Leverhulme Trust/ ; },
abstract = {Neanderthals occurred widely across north Eurasian landscapes, but between ~ 70 and 50 thousand years ago (ka) they expanded southwards into the Levant, which had previously been inhabited by Homo sapiens. Palaeoanthropological research in the first half of the twentieth century demonstrated alternate occupations of the Levant by Neanderthal and Homo sapiens populations, yet key early findings have largely been overlooked in later studies. Here, we present the results of new examinations of both the fossil and archaeological collections from Shukbah Cave, located in the Palestinian West Bank, presenting new quantitative analyses of a hominin lower first molar and associated stone tool assemblage. The hominin tooth shows clear Neanderthal affinities, making it the southernmost known fossil specimen of this population/species. The associated Middle Palaeolithic stone tool assemblage is dominated by Levallois reduction methods, including the presence of Nubian Levallois points and cores. This is the first direct association between Neanderthals and Nubian Levallois technology, demonstrating that this stone tool technology should not be considered an exclusive marker of Homo sapiens.},
}

@article {pmid33574596,
year = {2021},
author = {Remmel, A},
title = {Neanderthal-like 'mini-brains' created in lab with CRISPR.},
journal = {Nature},
volume = {590},
number = {7846},
pages = {376-377},
pmid = {33574596},
issn = {1476-4687},
mesh = {Brain ; Clustered Regularly Interspaced Short Palindromic Repeats ; DNA ; Humans ; *Neanderthals/genetics ; Stem Cells ; },
}

Brain
Clustered Regularly Interspaced Short Palindromic Repeats
DNA
Humans
*Neanderthals/genetics
Stem Cells

@article {pmid33574182,
year = {2021},
author = {Trujillo, CA and Rice, ES and Schaefer, NK and Chaim, IA and Wheeler, EC and Madrigal, AA and Buchanan, J and Preissl, S and Wang, A and Negraes, PD and Szeto, RA and Herai, RH and Huseynov, A and Ferraz, MSA and Borges, FS and Kihara, AH and Byrne, A and Marin, M and Vollmers, C and Brooks, AN and Lautz, JD and Semendeferi, K and Shapiro, B and Yeo, GW and Smith, SEP and Green, RE and Muotri, AR},
title = {Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment.},
journal = {Science (New York, N.Y.)},
volume = {371},
number = {6530},
pages = {},
pmid = {33574182},
issn = {1095-9203},
support = {R01 HL137223/HL/NHLBI NIH HHS/United States ; K12 GM068524/GM/NIGMS NIH HHS/United States ; U41 HG009889/HG/NHGRI NIH HHS/United States ; S10 OD026929/OD/NIH HHS/United States ; R01 HG004659/HG/NHGRI NIH HHS/United States ; R01 MH113545/MH/NIMH NIH HHS/United States ; K01 AA026911/AA/NIAAA NIH HHS/United States ; U19 MH107367/MH/NIMH NIH HHS/United States ; },
mesh = {Alleles ; Alternative Splicing ; Amino Acid Substitution ; Animals ; Binding Sites ; Biological Evolution ; CRISPR-Cas Systems ; Cell Proliferation ; Cerebral Cortex/cytology/*growth & development/*physiology ; Gene Expression Regulation, Developmental ; Genetic Variation ; Genome ; Genome, Human ; Haplotypes ; Hominidae/genetics ; Humans ; Induced Pluripotent Stem Cells ; Neanderthals/*genetics ; Nerve Net/physiology ; Nerve Tissue Proteins/genetics/metabolism ; Neurons/*physiology ; Organoids ; RNA-Binding Proteins/*genetics/*metabolism ; Synapses/physiology ; },
abstract = {The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 (NOVA1) plays a key role in neural development and function. NOVA1 also includes a protein-coding difference between the modern human genome and Neanderthal and Denisovan genomes. To investigate the functional importance of an amino acid change in humans, we reintroduced the archaic allele into human induced pluripotent cells using genome editing and then followed their neural development through cortical organoids. This modification promoted slower development and higher surface complexity in cortical organoids with the archaic version of NOVA1 Moreover, levels of synaptic markers and synaptic protein coassociations correlated with altered electrophysiological properties in organoids expressing the archaic variant. Our results suggest that the human-specific substitution in NOVA1, which is exclusive to modern humans since divergence from Neanderthals, may have had functional consequences for our species' evolution.},
}

Alleles
Alternative Splicing
Amino Acid Substitution
Animals
Binding Sites
Biological Evolution
CRISPR-Cas Systems
Cell Proliferation
Cerebral Cortex/cytology/*growth & development/*physiology
Gene Expression Regulation, Developmental
Genetic Variation
Genome
Genome, Human
Haplotypes
Hominidae/genetics
Humans
Induced Pluripotent Stem Cells
Neanderthals/*genetics
Nerve Net/physiology
Nerve Tissue Proteins/genetics/metabolism
Neurons/*physiology
Organoids
RNA-Binding Proteins/*genetics/*metabolism
Synapses/physiology

@article {pmid33568824,
year = {2021},
author = {Bergström, A and Stringer, C and Hajdinjak, M and Scerri, EML and Skoglund, P},
title = {Origins of modern human ancestry.},
journal = {Nature},
volume = {590},
number = {7845},
pages = {229-237},
pmid = {33568824},
issn = {1476-4687},
support = {/ERC_/European Research Council/International ; /WT_/Wellcome Trust/United Kingdom ; 217223/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; },
mesh = {Africa/ethnology ; Animals ; Fossils ; Gene Flow/genetics ; History, Ancient ; Human Migration/*history ; Humans ; Neanderthals/genetics ; *Pedigree ; },
abstract = {New finds in the palaeoanthropological and genomic records have changed our view of the origins of modern human ancestry. Here we review our current understanding of how the ancestry of modern humans around the globe can be traced into the deep past, and which ancestors it passes through during our journey back in time. We identify three key phases that are surrounded by major questions, and which will be at the frontiers of future research. The most recent phase comprises the worldwide expansion of modern humans between 40 and 60 thousand years ago (ka) and their last known contacts with archaic groups such as Neanderthals and Denisovans. The second phase is associated with a broadly construed African origin of modern human diversity between 60 and 300 ka. The oldest phase comprises the complex separation of modern human ancestors from archaic human groups from 0.3 to 1 million years ago. We argue that no specific point in time can currently be identified at which modern human ancestry was confined to a limited birthplace, and that patterns of the first appearance of anatomical or behavioural traits that are used to define Homo sapiens are consistent with a range of evolutionary histories.},
}

Africa/ethnology
Animals
Fossils
Gene Flow/genetics
History, Ancient
Human Migration/*history
Humans
Neanderthals/genetics
*Pedigree

@article {pmid33564646,
year = {2021},
author = {Mortazavi, SAR and Kaveh-Ahangar, K and Mortazavi, SMJ and Firoozi, D and Haghani, M},
title = {How Our Neanderthal Genes Affect the COVID-19 Mortality: Iran and Mongolia, Two Countries with the Same SARS-CoV-2 Mutation Cluster but Different Mortality Rates.},
journal = {Journal of biomedical physics & engineering},
volume = {11},
number = {1},
pages = {109-114},
pmid = {33564646},
issn = {2251-7200},
abstract = {Neanderthal genes possibly gave modern human protection against viruses. However, a recent study revealed that that a long sequence of DNA that is inherited from our Neanderthal ancestors can be linked to severe COVID-19 infection and hospitalization. Substantial evidence now indicates that our genetic background may be involved in the transmissibility of SARS-CoV-2 and the rapid progress of COVID-19 in some infected individuals. Although both morbidity and mortality of COVID-19 strongly depends on key factors such as age and co-existing health conditions, potential classes of human genomic variants possibly affect the likelihood of SARS-CoV-2 infection and its progress. Despite Iran and Mongolia seem to share the same SARS-CoV-2 mutation cluster, the COVID-19 mortality rates in these two countries are drastically different. While the population in Iran is 25.8 times higher than that of Mongolia, the number of confirmed cases is 1170 times higher. Moreover, the death rate shows a drastic difference. Since Neanderthals interbred with modern humans in Middle East between 47,000 and 65,000 years ago before going extinct 40,000 years ago, some Iranians have much more Neanderthal DNA than other people. Although neither genetic background nor environmental factors alone can determine our risk of developing severe COVID-19, our genes clearly affect both the development and progression of infectious diseases including COVID-19. Given these considerations, we believe that these great differences, at least to some extent, can be due to the proportion of Neanderthal genes among the people of these two countries.},
}

@article {pmid33556445,
year = {2021},
author = {Reinscheid, RK and Mafessoni, F and Lüttjohann, A and Jüngling, K and Pape, HC and Schulz, S},
title = {Neandertal introgression and accumulation of hypomorphic mutations in the neuropeptide S (NPS) system promote attenuated functionality.},
journal = {Peptides},
volume = {138},
number = {},
pages = {170506},
doi = {10.1016/j.peptides.2021.170506},
pmid = {33556445},
issn = {1873-5169},
abstract = {The neuropeptide S (NPS) system plays an important role in fear and fear memory processing but has also been associated with allergic and inflammatory diseases. Genes for NPS and its receptor NPSR1 are found in all tetrapods. Compared to non-human primates, several non-synonymous single-nucleotide polymorphisms (SNPs) occur in both human genes that collectively result in functional attenuation, suggesting adaptive mechanisms in a human context. To investigate historic and geographic origins of these hypomorphic mutations and explore genetic signs of selection, we analyzed ancient genomes and worldwide genotype frequencies of four prototypic SNPs in the NPS system. Neandertal and Denisovan genomes contain exclusively ancestral alleles for NPSR1 while all derived alleles occur in ancient genomes of anatomically modern humans, indicating that they arose in modern Homo sapiens. Worldwide genotype frequencies for three hypomorphic NPSR1 SNPs show significant regional homogeneity but follow a gradient towards increasing derived allele frequencies that supports an out-of-Africa scenario. Increased density of high-frequency polymorphisms around the three NPSR1 loci suggests weak or possibly balancing selection. A hypomorphic mutation in the NPS precursor, however, was detected at high frequency in Eurasian Neandertal genomes and shows genetic signatures indicating that it was introgressed into the human gene pool, particularly in Southern Europe, by interbreeding with Neandertals. We discuss potential evolutionary scenarios including behavior and immune-based natural selection.},
}

@article {pmid33547403,
year = {2021},
author = {Rampelli, S and Turroni, S and Mallol, C and Hernandez, C and Galván, B and Sistiaga, A and Biagi, E and Astolfi, A and Brigidi, P and Benazzi, S and Lewis, CM and Warinner, C and Hofman, CA and Schnorr, SL and Candela, M},
title = {Components of a Neanderthal gut microbiome recovered from fecal sediments from El Salt.},
journal = {Communications biology},
volume = {4},
number = {1},
pages = {169},
pmid = {33547403},
issn = {2399-3642},
support = {R01 GM089886/GM/NIGMS NIH HHS/United States ; },
abstract = {A comprehensive view of our evolutionary history cannot ignore the ancestral features of our gut microbiota. To provide some glimpse into the past, we searched for human gut microbiome components in ancient DNA from 14 archeological sediments spanning four stratigraphic units of El Salt Middle Paleolithic site (Spain), including layers of unit X, which has yielded well-preserved Neanderthal occupation deposits dating around 50 kya. According to our findings, bacterial genera belonging to families known to be part of the modern human gut microbiome are abundantly represented only across unit X samples, showing that well-known beneficial gut commensals, such as Blautia, Dorea, Roseburia, Ruminococcus, Faecalibacterium and Bifidobacterium already populated the intestinal microbiome of Homo since as far back as the last common ancestor between humans and Neanderthals.},
}

@article {pmid33543780,
year = {2021},
author = {Selig, KR and Kupczik, K and Silcox, MT},
title = {The effect of high wear diets on the relative pulp volume of the lower molars.},
journal = {American journal of physical anthropology},
volume = {174},
number = {4},
pages = {804-811},
doi = {10.1002/ajpa.24242},
pmid = {33543780},
issn = {1096-8644},
abstract = {OBJECTIVES: One role of dental pulp is in the upkeep and maintenance of dentine. Under wear, odontoblasts in the pulp deposit tertiary dentine to ensure the sensitive internal dental tissues are not exposed and vulnerable to infection. It follows that there may be an adaptive advantage for increasing molar pulp volume in anthropoid primate taxa that are prone to high levels of wear. The relative volume of dental pulp is therefore predicted to covary with dietary abrasiveness (in the sense of including foods that cause high degrees of wear).

MATERIALS AND METHODS: We examined relatively unworn lower second molars in pairs of species of extant hominoids, cebids, and pitheciids that vary in the abrasiveness of their diet (n = 36). Using micro-CT scans, we measured the percent of tooth that is pulp (PTP) as the ratio of pulp volume to that of the total volume of the tooth.

RESULTS: We found that in each pair of species, the taxa that consume a more abrasive diet had a significantly higher PTP than the closely related taxa that consume a softer diet.

CONCLUSIONS: Our results point to an adaptive mechanism in the molars of taxa that consume abrasive diets and are thus subject to higher levels of wear. Our results provide additional understanding of the relationship between dental pulp and diet and may offer insight into the diet of extinct taxa such as Paranthropus boisei or into the adaptive context of the taurodont molars of Neanderthals.},
}

@article {pmid33524842,
year = {2021},
author = {Lacy, SA},
title = {Evidence of dental agenesis in late pleistocene Homo.},
journal = {International journal of paleopathology},
volume = {32},
number = {},
pages = {103-110},
doi = {10.1016/j.ijpp.2021.01.001},
pmid = {33524842},
issn = {1879-9825},
abstract = {OBJECTIVE: Differential diagnosis and tabulation of cases of dental agenesis in Middle and Upper Paleolithic Western Eurasian humans to synthesize this data and to test previous hypotheses about when recent human patterns of third molar agenesis were established.

MATERIALS: 139 Late Pleistocene human remains and 149 individuals from three Epi-Paleolithic/ Holocene non-agricultural comparative collections.

METHODS: All remains were visually and radiographically recorded by the author.

RESULTS: In addition to establishing that third molar agenesis was common during the Late Upper Paleolithic (22,500-10,000 years BP), this study suggests a pattern of increasing prevalence through time.

CONCLUSIONS: An increase in the prevalence of third molar agenesis in the Late Upper Paleolithic could indicate selection for dental size reduction and orthognathy, but also bio-cultural changes from more intensive food preparation techniques.

SIGNIFICANCE: Third molar agenesis, a well-known developmental defect, is often reported for recent human skeletal collections, but the prevalence of the condition for Pleistocene hominins had not been previously quantified in order to consider patterns through time. Hypotheses posited for the high prevalence of third molar agenesis, or hypodontia in general, in some recent human groups require an understanding of the prevalence of these traits in the past.

LIMITATIONS: Paleolithic skeletal remains are incomplete, so these values are under-estimations. Individuals are also separated diachronically and geographically and should not be assumed to represent a single population sample.

Hypotheses on some of the potential selective forces acting on dental size reduction and subsequent agenesis could be tested in recent humans.},
}

@article {pmid33517134,
year = {2021},
author = {Compton, T and Skinner, MM and Humphrey, L and Pope, M and Bates, M and Davies, TW and Parfitt, SA and Plummer, WP and Scott, B and Shaw, A and Stringer, C},
title = {The morphology of the Late Pleistocene hominin remains from the site of La Cotte de St Brelade, Jersey (Channel Islands).},
journal = {Journal of human evolution},
volume = {152},
number = {},
pages = {102939},
doi = {10.1016/j.jhevol.2020.102939},
pmid = {33517134},
issn = {1095-8606},
abstract = {Thirteen permanent fully erupted teeth were excavated at the Paleolithic site of La Cotte de St Brelade in Jersey in 1910 and 1911. These were all found in the same location, on a ledge behind a hearth in a Mousterian occupation level. They were originally identified as being Neanderthal. A fragment of occipital bone was found in a separate locality in a later season. Recent dating of adjacent sediments gives a probable age of <48 ka. The purpose of this article is to provide an updated description of the morphology of this material and consider its likely taxonomic assignment from comparison with Neanderthal and Homo sapiens samples. One of the original teeth has been lost, and we identify one as nonhominin. At least two adult individuals are represented. Cervix shape and the absence of common Neanderthal traits in several teeth suggest affinities with H. sapiens in both individuals, while crown and root dimensions and root morphology of all the teeth are entirely consistent with a Neanderthal attribution, pointing toward a possible shared Neanderthal and H. sapiens ancestry (the likely date of this material corresponds with the time in which both Neanderthals and H. sapiens were present in Europe). The occipital fragment is stratigraphically more recent and does not exhibit any diagnostic Neanderthal features.},
}

@article {pmid33486494,
year = {2021},
author = {Kliesch, S and Schmidt, S and Wilborn, D and Aigner, C and Albrecht, W and Bedke, J and Beintker, M and Beyersdorff, D and Bokemeyer, C and Busch, J and Classen, J and de Wit, M and Dieckmann, KP and Diemer, T and Dieing, A and Gockel, M and Göckel-Beining, B and Hakenberg, OW and Heidenreich, A and Heinzelbecker, J and Herkommer, K and Hermanns, T and Kaufmann, S and Kornmann, M and Kotzerke, J and Krege, S and Kristiansen, G and Lorch, A and Müller, AC and Oechsle, K and Ohloff, T and Oing, C and Otto, U and Pfister, D and Pichler, R and Recken, H and Rick, O and Rudolph, Y and Ruf, C and Schirren, J and Schmelz, H and Schmidberger, H and Schrader, M and Schweyer, S and Seeling, S and Souchon, R and Winter, C and Wittekind, C and Zengerling, F and Zermann, DH and Zillmann, R and Albers, P},
title = {Management of Germ Cell Tumours of the Testes in Adult Patients: German Clinical Practice Guideline, PART II - Recommendations for the Treatment of Advanced, Recurrent, and Refractory Disease and Extragonadal and Sex Cord/Stromal Tumours and for the Management of Follow-Up, Toxicity, Quality of Life, Palliative Care, and Supportive Therapy.},
journal = {Urologia internationalis},
volume = {105},
number = {3-4},
pages = {181-191},
pmid = {33486494},
issn = {1423-0399},
abstract = {OBJECTIVES: We developed the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up of germ cell tumours (GCT) of the testes in adult patients. We present the guideline content in 2 separate publications. The present second part summarizes therecommendations for the treatment of advanced disease stages and for the management of follow-up and late effects.

MATERIALS AND METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search in March 2018), were provided. Thirty-one experts, who were entitled to vote, rated the final clinical recommendations and statements.

RESULTS: Here we present the treatment recommendations separately for patients with metastatic seminoma and non-seminomatous GCT (stages IIA/B and IIC/III), for restaging and treatment of residual masses, and for relapsed and refractory disease stages. The recommendations also cover extragonadal and sex cord/stromal tumours, the management of follow-up and toxicity, quality-of-life aspects, palliative care, and supportive therapy.

CONCLUSION: Physicians and other medical service providers who are involved in the diagnostics, treatment, and follow-up of GCT (all stages, outpatient and inpatient care as well as rehabilitation) are the users of the present guideline. The guideline also comprises quality indicators for measuring the implementation of the guideline recommendations in routine clinical care; these data will be presented in a future publication.},
}

@article {pmid33459351,
year = {2020},
author = {VanSickle, C and Cofran, Z and Hunt, D},
title = {Did Neandertals have large brains? Factors affecting endocranial volume comparisons.},
journal = {American journal of physical anthropology},
volume = {173},
number = {4},
pages = {768-775},
doi = {10.1002/ajpa.24124},
pmid = {33459351},
issn = {1096-8644},
mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Anthropology, Physical ; Brain/*anatomy & histology ; Cephalometry ; Female ; Fossils ; Humans ; Male ; Middle Aged ; Neanderthals/*anatomy & histology ; Sex Characteristics ; Skull/*anatomy & histology ; Young Adult ; },
abstract = {OBJECTIVES: Common wisdom in paleoanthropology is that Neandertals had bigger brains than recent humans. Here we tested the hypothesis that there is no difference in brain size between Neandertals and recent humans while accounting for methodological variation and the makeup of both the Neandertal and recent human samples.

MATERIALS AND METHODS: We examined endocranial volume (ECV) derived from virtually reconstructed endocasts of 11 Neandertals, six of which had associated femoral head diameters (FHD). Our recent human comparative dataset consisted of virtually measured ECV and associated FHD from 94 recent humans from the Robert J. Terry Anatomical Collection (63 male, 31 female). ECV of Neandertals and recent humans was compared using bootstrap resampling, repeating the analysis for two groupings of Neandertals (all and classic) and for three groupings of recent humans (all, males, and females). To examine brain size scaling, we completed an ordinary least squares regression of log (ECV) against log (FHD) for Neandertals and recent humans.

RESULTS: The results of the bootstrap resampling analyses indicated that Neandertals only had significantly larger ECV when compared with recent human females. The regression between ECV and FHD suggested that Neandertals fall within the range of variation for larger humans.

DISCUSSION: Our results demonstrate that Neandertals do not have uniquely large brains when compared with recent humans. Their brain size falls in the large end of the recent human range of variation, but does not exceed it. These results have implications for future research on Neandertal encephalization.},
}

Adult
Aged
Aged, 80 and over
Animals
Anthropology, Physical
Brain/*anatomy & histology
Cephalometry
Female
Fossils
Humans
Male
Middle Aged
Neanderthals/*anatomy & histology
Sex Characteristics
Skull/*anatomy & histology
Young Adult

@article {pmid33454959,
year = {2021},
author = {Towle, I and Loch, C},
title = {Tooth chipping prevalence and patterns in extant primates.},
journal = {American journal of physical anthropology},
volume = {175},
number = {1},
pages = {292-299},
doi = {10.1002/ajpa.24232},
pmid = {33454959},
issn = {1096-8644},
support = {//University of Otago/ ; },
abstract = {OBJECTIVES: A tooth chip occurs when a hard object forcefully contacts the surface of the tooth, typically removing enamel from the occlusal edge. In this study, chipping patterns in extant primates were compared, and hard-object-feeding assessed alongside other factors (e.g., grit mastication and dental properties), to elucidate dietary and behavioral inferences in archeological and paleontological samples.

MATERIALS AND METHODS: Thirteen species of extant primates were studied, including eight species within the Cercopithecidae, two within the Ceboidea, and three within the Hominoidea. Four additional species were also incorporated from the literature for some of the analyses. The severity (Grade 1-3), position (buccal, lingual, mesial, and distal) and number of tooth fractures were recorded for each specimen.

RESULTS: Species considered hard-object-feeding specialists presented higher rates of chipping, with sakis, mandrills, sooty mangabeys and Raffles' banded langurs having high chipping rates (28.3%, 36.7%, 48.4%, and 34.7% of teeth, respectively). Species that seasonally eat harder foods had intermediate chipping frequencies (e.g., brown woolly monkeys: 18.5%), and those that less commonly consume hard food items had the lowest chipping frequencies (e.g., Kloss gibbon: 7.3%; chimpanzees: 4.4%).

DISCUSSION: The results suggest hard food mastication influences differences in chipping prevalence among the species studied. Although Homo fossil samples show high rates of chipping comparable to hard-object-feeding extant primates, they display a different pattern of chipping, supporting the hypothesis that these fractures are mostly non-food related (e.g., grit mastication in Homo naledi; non-masticatory tooth use in Neanderthals).},
}

@article {pmid33446842,
year = {2021},
author = {Pederzani, S and Aldeias, V and Dibble, HL and Goldberg, P and Hublin, JJ and Madelaine, S and McPherron, SP and Sandgathe, D and Steele, TE and Turq, A and Britton, K},
title = {Reconstructing Late Pleistocene paleoclimate at the scale of human behavior: an example from the Neandertal occupation of La Ferrassie (France).},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {1419},
pmid = {33446842},
issn = {2045-2322},
support = {RPG-2017-410//Leverhulme Trust/ ; },
abstract = {Exploring the role of changing climates in human evolution is currently impeded by a scarcity of climatic information at the same temporal scale as the human behaviors documented in archaeological sites. This is mainly caused by high uncertainties in the chronometric dates used to correlate long-term climatic records with archaeological deposits. One solution is to generate climatic data directly from archaeological materials representing human behavior. Here we use oxygen isotope measurements of Bos/Bison tooth enamel to reconstruct summer and winter temperatures in the Late Pleistocene when Neandertals were using the site of La Ferrassie. Our results indicate that, despite the generally cold conditions of the broader period and despite direct evidence for cold features in certain sediments at the site, Neandertals used the site predominantly when climatic conditions were mild, similar to conditions in modern day France. We suggest that due to millennial scale climate variability, the periods of human activity and their climatic characteristics may not be representative of average conditions inferred from chronological correlations with long-term climatic records. These results highlight the importance of using direct routes, such as the high-resolution archives in tooth enamel from anthropogenically accumulated faunal assemblages, to establish climatic conditions at a human scale.},
}

@article {pmid33441416,
year = {2021},
author = {Dumas, G and Malesys, S and Bourgeron, T},
title = {Systematic detection of brain protein-coding genes under positive selection during primate evolution and their roles in cognition.},
journal = {Genome research},
volume = {31},
number = {3},
pages = {484-496},
pmid = {33441416},
issn = {1549-5469},
abstract = {The human brain differs from that of other primates, but the genetic basis of these differences remains unclear. We investigated the evolutionary pressures acting on almost all human protein-coding genes (N = 11,667; 1:1 orthologs in primates) based on their divergence from those of early hominins, such as Neanderthals, and non-human primates. We confirm that genes encoding brain-related proteins are among the most strongly conserved protein-coding genes in the human genome. Combining our evolutionary pressure metrics for the protein-coding genome with recent data sets, we found that this conservation applied to genes functionally associated with the synapse and expressed in brain structures such as the prefrontal cortex and the cerebellum. Conversely, several genes presenting signatures commonly associated with positive selection appear as causing brain diseases or conditions, such as micro/macrocephaly, Joubert syndrome, dyslexia, and autism. Among those, a number of DNA damage response genes associated with microcephaly in humans such as BRCA1, NHEJ1, TOP3A, and RNF168 show strong signs of positive selection and might have played a role in human brain size expansion during primate evolution. We also showed that cerebellum granule neurons express a set of genes also presenting signatures of positive selection and that may have contributed to the emergence of fine motor skills and social cognition in humans. This resource is available online and can be used to estimate evolutionary constraints acting on a set of genes and to explore their relative contributions to human traits.},
}

@article {pmid33436796,
year = {2021},
author = {McGrath, K and Limmer, LS and Lockey, AL and Guatelli-Steinberg, D and Reid, DJ and Witzel, C and Bocaege, E and McFarlin, SC and El Zaatari, S},
title = {3D enamel profilometry reveals faster growth but similar stress severity in Neanderthal versus Homo sapiens teeth.},
journal = {Scientific reports},
volume = {11},
number = {1},
pages = {522},
pmid = {33436796},
issn = {2045-2322},
support = {798117//H2020 Marie Skłodowska-Curie Actions/ ; EB Fellowship//British Academy/ ; 353106138//Deutsche Forschungsgemeinschaft/ ; },
abstract = {Early life stress disrupts growth and creates horizontal grooves on the tooth surface in humans and other mammals, yet there is no consensus for their quantitative analysis. Linear defects are considered to be nonspecific stress indicators, but evidence suggests that intermittent, severe stressors create deeper defects than chronic, low-level stressors. However, species-specific growth patterns also influence defect morphology, with faster-growing teeth having shallower defects at the population level. Here we describe a method to measure the depth of linear enamel defects and normal growth increments (i.e., perikymata) from high-resolution 3D topographies using confocal profilometry and apply it to a diverse sample of Homo neanderthalensis and H. sapiens anterior teeth. Debate surrounds whether Neanderthals exhibited modern human-like growth patterns in their teeth and other systems, with some researchers suggesting that they experienced more severe childhood stress. Our results suggest that Neanderthals have shallower features than H. sapiens from the Upper Paleolithic, Neolithic, and medieval eras, mirroring the faster growth rates in Neanderthal anterior teeth. However, when defect depth is scaled by perikymata depth to assess their severity, Neolithic humans have less severe defects, while Neanderthals and the other H. sapiens groups show evidence of more severe early life growth disruptions.},
}

@article {pmid33429259,
year = {2021},
author = {Heydari, M and Guérin, G and Zeidi, M and Conard, NJ},
title = {Bayesian luminescence dating at Ghār-e Boof, Iran, provides a new chronology for Middle and Upper Paleolithic in the southern Zagros.},
journal = {Journal of human evolution},
volume = {151},
number = {},
pages = {102926},
doi = {10.1016/j.jhevol.2020.102926},
pmid = {33429259},
issn = {1095-8606},
abstract = {Ghār-e Boof is a Paleolithic cave site in Iran well known for its rich early Upper Paleolithic Rostamian assemblages. The site is located on the edge of the Dasht-e Rostam plain in the southern Zagros. Recent excavations by the members of the Tübingen-Iranian Stone Age Research Project at Ghār-e Boof also recovered well-stratified Middle Paleolithic assemblages. Here, we provide the first detailed luminescence chronology for the Middle and Upper Paleolithic of the site. More generally, our work is the first luminescence chronology for a Middle and Upper Paleolithic site in the Zagros Mountains region in Iran. The luminescence ages for the Upper Paleolithic of Ghār-e Boof agree with published 14C dates. We applied Bayesian models specifically designed for luminescence dating using the R package 'BayLum' to incorporate the well-established stratigraphic constraints, as well as the published 14C ages with our optically stimulated luminescence (OSL) ages to improve the precision of the chronological framework. The Bayesian chronology shows a significantly improved precision of the OSL ages in particular for the upper part of the sequence where 14C ages were available. The Bayesian OSL ages for the Rostamian horizons, archaeologicalhorizon (AH) III (a-b-c), and AH IV, fall in the range of 37-42 ka (68% credible interval [CI]). Moreover, we determined a series of dates between 45 and 81 ka (68% CI) for the Middle Paleolithic strata from AH IVd to AH VI. Our results point to a demographic shift in the populations responsible for the Middle Paleolithic and the Rostamian within three millennia. This major technological change accompanied by the rise of symbolic artifacts such as personal ornaments, may or may not reflect a replacement of Neanderthals by modern humans. While we are confident that the Rostamian was made by modern humans, available information does not allow us to be sure who made the local Middle Paleolithic.},
}

@article {pmid33418451,
year = {2021},
author = {Nowaczewska, W and Binkowski, M and Benazzi, S and Vazzana, A and Nadachowski, A and Stefaniak, K and Żarski, M and Talamo, S and Compton, T and Stringer, CB and Hajdinjak, M and Hublin, JJ},
title = {New hominin teeth from Stajnia Cave, Poland.},
journal = {Journal of human evolution},
volume = {151},
number = {},
pages = {102929},
doi = {10.1016/j.jhevol.2020.102929},
pmid = {33418451},
issn = {1095-8606},
}

@article {pmid33417716,
year = {2021},
author = {Greer, C and Bhakta, H and Ghanem, L and Refai, F and Linn, E and Avella, M},
title = {Deleterious variants in genes regulating mammalian reproduction in Neanderthals, Denisovans and extant humans.},
journal = {Human reproduction (Oxford, England)},
volume = {36},
number = {3},
pages = {734-755},
doi = {10.1093/humrep/deaa347},
pmid = {33417716},
issn = {1460-2350},
abstract = {STUDY QUESTION: Were Neanderthals and Denisovans (referred here also as extinct hominidae) carrying deleterious variants in genes regulating reproduction?

SUMMARY ANSWER: The majority of extinct hominidae analyzed here, presented a considerable number of deleterious variants per individual in proteins regulating different aspects of reproduction, including gonad and uterine function, and gametogenesis.

WHAT IS KNOWN ALREADY: Neanderthals, Denisovans and extant humans were interfertile and hybridized while occupying geographically overlapping areas in Europe and Asia. This is evidenced by the small archaic genome component (average ∼2%) present in non-African extant humans.

STUDY DESIGN, SIZE, DURATION: The genome of eight extinct hominidae, together with five human genome databases, plus 44 mothers and 48 fathers (fertile controls), were screened to look for deleterious variants in 1734 protein-coding genes regulating reproduction.

Ancient DNA from six Neanderthals and two Denisovans dated between ∼82 000 and 43 000 calibrated years was retrieved from the public European Nucleotide Archive. The hominins analyzed include Altai, Vindija 33.15, 33.19, 33.25 and 33.26, El Sidron 1253, Denisova 3 and 11. Their DNA was analyzed using the CLC Genomics Workbench 12, by mapping overlapping paired-end reads (Illumina, FASTQ files) to the human genome assembly GRCh37 (hg19) (Vindija 33.19, 33.25, 33.26, Denisova 3 and Denisova 11) or by analyzing BAM files (Altai, El Sidron 1253 and Vindija 33.15) (human genome reference, GRCh37 (hg19)). Non-synonymous reproductive variants were classified as deleterious or tolerated (PolyPhen-2 and SIFT analyses) and were compared to deleterious variants obtained from extant human genome databases (Genome Aggregation Database (GnomAD), 1000 Genomes, the Haplotype Map (HapMap), Single Nucleotide Polymorphism Database (dbSNPs)) across different populations. A genetic intersection between extant or extinct DNA variants and other genetic disorders was evaluated by annotating the obtained variants with the Clinical Variant (ClinVar) database.

Among the eight extinct hominidae analyzed, a total of 9650 non-synonymous variants (only coverage ≥20 reads included; frameshift mutations were excluded) in 1734 reproductive protein-coding genes were found, 24% of which were classified as deleterious. The majority (73%) of the deleterious alleles present in extant humans that are shared between extant humans and extinct hominidae were found to be rare (<1%) in extant human populations. A set of 8044 variants were found uniquely in extinct hominidae. At the single-gene level, no extinct individual was found to be homozygous for deleterious variants in genes necessary for gamete recognition and fusion, and no higher chance of embryo-lethality (calculated by Mendelian Genetics) was found upon simulated mating between extant human and extinct hominidae compared to extant human-extant human. However, three of the eight extinct hominidae were found to be homozygous for 48-69 deleterious variants in 55 genes controlling ovarian and uterine functions, or oogenesis (AKAP1, BUB1B, CCDC141, CDC73, DUSP6, ESR1, ESR2, PATL2, PSMC3IP, SEMA3A, WT1 and WNT4). Moreover, we report the distribution of nine Neanderthal variants in genes associated with a human fertility phenotype found in extant human populations, one of which has been associated with polycystic ovarian syndrome and primary congenital glaucoma.

While analyzing archaic DNA, stringent filtering criteria were adopted to screen for deleterious variants in Neanderthals and Denisovans, which could result in missing a number of variants. Such restraints preserve the potential for detection of additional deleterious variants in reproductive proteins in extinct hominidae.

This study provides a comprehensive overview of putatively deleterious variants in extant human populations and extinct individuals occurring in 1734 protein-coding genes controlling reproduction and provides the fundaments for future functional studies of extinct variants in human reproduction.

This study was supported by the Department of Biological Science and by the Office of Research and Sponsored Programs at the University of Tulsa (Faculty Research Grant and Faculty Research Summer Fellowship) to M.A. and the University of Tulsa, Tulsa Undergraduate Research Challenge (TURC) program to E.L.; no conflict of interest to declare.

TRIAL REGISTRATION NUMBER: N/A.},
}

@article {pmid33412555,
year = {2021},
author = {Kliesch, S and Schmidt, S and Wilborn, D and Aigner, C and Albrecht, W and Bedke, J and Beintker, M and Beyersdorff, D and Bokemeyer, C and Busch, J and Classen, J and de Wit, M and Dieckmann, KP and Diemer, T and Dieing, A and Gockel, M and Göckel-Beining, B and Hakenberg, OW and Heidenreich, A and Heinzelbecker, J and Herkommer, K and Hermanns, T and Kaufmann, S and Kornmann, M and Kotzerke, J and Krege, S and Kristiansen, G and Lorch, A and Müller, AC and Oechsle, K and Ohloff, T and Oing, C and Otto, U and Pfister, D and Pichler, R and Recken, H and Rick, O and Rudolph, Y and Ruf, C and Schirren, J and Schmelz, H and Schmidberger, H and Schrader, M and Schweyer, S and Seeling, S and Souchon, R and Winter, C and Wittekind, C and Zengerling, F and Zermann, DH and Zillmann, R and Albers, P},
title = {Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.},
journal = {Urologia internationalis},
volume = {105},
number = {3-4},
pages = {169-180},
pmid = {33412555},
issn = {1423-0399},
abstract = {INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages.

METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements.

RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma.

CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.},
}

@article {pmid33412453,
year = {2021},
author = {Dodat, PJ and Tacail, T and Albalat, E and Gómez-Olivencia, A and Couture-Veschambre, C and Holliday, T and Madelaine, S and Martin, JE and Rmoutilova, R and Maureille, B and Balter, V},
title = {Isotopic calcium biogeochemistry of MIS 5 fossil vertebrate bones: application to the study of the dietary reconstruction of Regourdou 1 Neandertal fossil.},
journal = {Journal of human evolution},
volume = {151},
number = {},
pages = {102925},
doi = {10.1016/j.jhevol.2020.102925},
pmid = {33412453},
issn = {1095-8606},
abstract = {The calcium isotopic composition (δ44/42Ca) of bone and tooth enamel can be used for dietary reconstructions of extant and extinct mammals. In natural conditions, the δ44/42Ca value of bone and teeth varies according to dietary intake with a constant isotopic offset of about -0.6‰. Owing to the poor conservation of collagen, carbon (C), and nitrogen (N) isotopic compositions of the Regourdou Mousterian site (MIS 5, Dordogne, France) previously failed to provide any paleodietary information. Therefore, to reconstruct the trophic chain, we have measured calcium (Ca) isotopes from fossil bone samples of the fauna from the Regourdou site, as well as from three bone samples of the Regourdou 1 Neandertal specimen. The results show a taxon-dependent patterning of the Ca isotopic compositions: herbivores generally have higher δ44/42Ca values than carnivores. All the δ44/42Ca values of Regourdou 1 are low (<-1.6‰), placing this specimen amid carnivores. Using a bone-muscle Ca isotopic offset determined on extant animals, we further show that the δ44/42Ca value of the Regourdou 1 diet, and that of most carnivores, cannot be accounted for by the consumption of meat only, as plants and meat have indistinguishable δ44/42Ca values. Mass balance calculations indicate that the low δ44/42Ca values of the Neandertal's carnivorous diet are explained by the ingestion of bone marrow containing as little as 1% trabecular bone. Our results show that the Regourdou 1 Neanderthal consumed a mixture of various herbivorous prey, as well as trabecular bone, which probably occurred when marrow was ingested, by accident or intentionally.},
}

@article {pmid33362257,
year = {2020},
author = {González-Molina, I and Jiménez-García, B and Maíllo-Fernández, JM and Baquedano, E and Domínguez-Rodrigo, M},
title = {Distinguishing Discoid and Centripetal Levallois methods through machine learning.},
journal = {PloS one},
volume = {15},
number = {12},
pages = {e0244288},
pmid = {33362257},
issn = {1932-6203},
mesh = {Algorithms ; Animals ; Archaeology/*methods ; Fossils/*diagnostic imaging ; Hominidae ; Humans ; Inventions ; Machine Learning ; Neanderthals ; Technology ; Tool Use Behavior/*classification ; },
abstract = {In this paper, we apply Machine Learning (ML) algorithms to study the differences between Discoid and Centripetal Levallois methods. For this purpose, we have used experimentally knapped flint flakes, measuring several parameters that have been analyzed by seven ML algorithms. From these analyses, it has been possible to demonstrate the existence of statistically significant differences between Discoid products and Centripetal Levallois products, thus contributing with new data and a new method to this traditional debate. The new approach enabled differentiating the blanks created by both knapping methods with an accuracy >80% using only ten typometric variables. The most relevant variables were maximum length, width to the 25%, 50% and 75% of the flake length, external and internal platform angles, maximum width and number of dorsal scars. This study also demonstrates the advantages of the application of multivariate ML methods to lithic studies.},
}

Algorithms
Animals
Archaeology/*methods
Fossils/*diagnostic imaging
Hominidae
Humans
Inventions
Machine Learning
Neanderthals
Technology
Tool Use Behavior/*classification

@article {pmid33360685,
year = {2021},
author = {Adegboyega, MT and Stamos, PA and Hublin, JJ and Weaver, TD},
title = {Virtual reconstruction of the Kebara 2 Neanderthal pelvis.},
journal = {Journal of human evolution},
volume = {151},
number = {},
pages = {102922},
doi = {10.1016/j.jhevol.2020.102922},
pmid = {33360685},
issn = {1095-8606},
abstract = {The paucity of well-preserved pelvises in the hominin fossil record has hindered robust analyses of shifts in critical biological processes throughout human evolution. The Kebara 2 pelvis remains one of the best preserved hominin pelvises, providing a rare opportunity to assess Neanderthal pelvic morphology and function. Here, we present two new reconstructions of the Kebara 2 pelvis created from CT scans of the right hip bone and sacrum. For both reconstructions, we proceeded as follows. First, we virtually reconstructed the right hip bone and the sacrum by repositioning the fragments of the hip bone and sacrum. Then, we created a mirrored copy of the right hip bone to act as the left hip bone. Next, we 3D printed the three bones and physically articulated them. Finally, we used fiducial points collected from the physically articulated models to articulate the hip bones and sacrum in virtual space. Our objectives were to (1) reposition misaligned fragments, particularly the ischiopubic ramus; (2) create a 3D model of a complete pelvis; and (3) assess interobserver reconstruction variation. These new reconstructions show that, in comparison with previous measurements, Kebara 2 possessed a higher shape index (maximum anteroposterior length/maximum mediolateral width) for the pelvic inlet and perhaps the outlet and a more anteriorly positioned sacral promontory and pubic symphysis relative to the acetabula. The latter differences result in a lower ratio between the distances anterior and posterior to the anterior margins of the acetabula. Generally, the new reconstructions tend to accentuate features of the Kebara 2 pelvis--the long superior pubic ramus and anteriorly positioned pelvic inlet--that have already been discussed for Kebara 2 and other Neanderthals.},
}

@article {pmid33356949,
year = {2020},
author = {Higgitt, R},
title = {Neanderthal and the fossilization of the Third World.},
journal = {Social studies of science},
volume = {},
number = {},
pages = {306312720983460},
doi = {10.1177/0306312720983460},
pmid = {33356949},
issn = {1460-3659},
abstract = {Neanderthal is the quintessential scientific Other. In the late nineteenth century gentlemen-scientists, including business magnates, investment bankers and lawmakers with interest in questions of human and human societal development, framed Europe's Neanderthal and South Asia's indigenous Negritos as close evolutionary kin. Simultaneously, they explained Neanderthal's extinction as the consequence of an inherent backwardness in the face of fair-skinned, steadily-progressing newcomers to ancient Europe who behaved in ways associated with capitalism. This racialization and economization of Neanderthal helped bring meaning and actual legal reality to Negritos via the British Raj's official 'schedules of backward castes and tribes'. It also helped justify the Raj's initiation of market-oriented reforms in order to break a developmental equilibrium deemed created when fair-skinned newcomers to ancient South Asia enslaved Negritos in an enduring caste system. Neanderthal was integral to the scientism behind the British construction of caste, and contributed to India's becoming a principal 'Third World' target of Western structural adjustment policies as continuation of South Asia's 'evolution assistance'.},
}

@article {pmid33343925,
year = {2020},
author = {Kist, NC and Lambert, B and Campbell, S and Katzourakis, A and Lunn, D and Lemey, P and Iversen, AKN},
title = {HIV-1 p24Gag adaptation to modern and archaic HLA-allele frequency differences in ethnic groups contributes to viral subtype diversification.},
journal = {Virus evolution},
volume = {6},
number = {2},
pages = {veaa085},
pmid = {33343925},
issn = {2057-1577},
abstract = {Pathogen-driven selection and past interbreeding with archaic human lineages have resulted in differences in human leukocyte antigen (HLA)-allele frequencies between modern human populations. Whether or not this variation affects pathogen subtype diversification is unknown. Here we show a strong positive correlation between ethnic diversity in African countries and both human immunodeficiency virus (HIV)-1 p24gag and subtype diversity. We demonstrate that ethnic HLA-allele differences between populations have influenced HIV-1 subtype diversification as the virus adapted to escape common antiviral immune responses. The evolution of HIV Subtype B (HIV-B), which does not appear to be indigenous to Africa, is strongly affected by immune responses associated with Eurasian HLA variants acquired through adaptive introgression from Neanderthals and Denisovans. Furthermore, we show that the increasing and disproportionate number of HIV-infections among African Americans in the USA drive HIV-B evolution towards an Africa-centric HIV-1 state. Similar adaptation of other pathogens to HLA variants common in affected populations is likely.},
}

@article {pmid33341120,
year = {2020},
author = {Árnason, Ú and Hallström, B},
title = {The reversal of human phylogeny: Homo left Africa as erectus, came back as sapiens sapiens.},
journal = {Hereditas},
volume = {157},
number = {1},
pages = {51},
pmid = {33341120},
issn = {1601-5223},
support = {2018//Kungliga Fysiografiska Sällskapet i Lund (SE)/ ; 2018//Erik Philip Sörensens Foundation (SE)/ ; },
abstract = {BACKGROUND: The molecular out of Africa hypothesis, OOAH, has been considered as an established fact amid population geneticists for some 25-30 years despite the early concern with it among phylogeneticists with experience beyond that of Homo. The palaeontological support for the hypothesis is also questionable, a circumstance that in the light of expanding Eurasian palaeontological knowledge has become accentuated through the last decades.

RESULTS: The direction of evolution in the phylogenetic tree of modern humans (Homo sapiens sapiens, Hss) was established inter alia by applying progressive phylogenetic analysis to an mtDNA sampling that included a Eurasian, Lund, and the African Mbuti, San and Yoruba. The examination identified the African populations as paraphyletic, thereby compromising the OOAH. The finding, which was consistent with the out of Eurasia hypothesis, OOEH, was corroborated by the mtDNA introgression from Hss into Hsnn (Neanderthals) that demonstrated the temporal and physical Eurasian coexistence of the two lineages. The results are consistent with the palaeontologically established presence of H. erectus in Eurasia, a Eurasian divergence between H. sapiens and H. antecessor ≈ 850,000 YBP, an Hs divergence between Hss and Hsn (Neanderthals + Denisovans) ≈ 800,000 YBP, an mtDNA introgression from Hss into Hsnn* ≈ 500,000 YBP and an Eurasian divergence among the ancestors of extant Hss ≈ 250,000 YBP at the exodus of Mbuti/San into Africa.

CONCLUSIONS: The present study showed that Eurasia was not the receiver but the donor in Hss evolution. The findings that Homo left Africa as erectus and returned as sapiens sapiens constitute a change in the understanding of Hs evolution to one that conforms to the extensive Eurasian record of Hs palaeontology and archaeology.},
}

@article {pmid33299013,
year = {2020},
author = {Balzeau, A and Turq, A and Talamo, S and Daujeard, C and Guérin, G and Welker, F and Crevecoeur, I and Fewlass, H and Hublin, JJ and Lahaye, C and Maureille, B and Meyer, M and Schwab, C and Gómez-Olivencia, A},
title = {Pluridisciplinary evidence for burial for the La Ferrassie 8 Neandertal child.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {21230},
pmid = {33299013},
issn = {2045-2322},
abstract = {The origin of funerary practices has important implications for the emergence of so-called modern cognitive capacities and behaviour. We provide new multidisciplinary information on the archaeological context of the La Ferrassie 8 Neandertal skeleton (grand abri of La Ferrassie, Dordogne, France), including geochronological data -14C and OSL-, ZooMS and ancient DNA data, geological and stratigraphic information from the surrounding context, complete taphonomic study of the skeleton and associated remains, spatial information from the 1968-1973 excavations, and new (2014) fieldwork data. Our results show that a pit was dug in a sterile sediment layer and the corpse of a two-year-old child was laid there. A hominin bone from this context, identified through Zooarchaeology by Mass Spectrometry (ZooMS) and associated with Neandertal based on its mitochondrial DNA, yielded a direct 14C age of 41.7-40.8 ka cal BP (95%), younger than the 14C dates of the overlying archaeopaleontological layers and the OSL age of the surrounding sediment. This age makes the bone one of the most recent directly dated Neandertals. It is consistent with the age range for the Châtelperronian in the site and in this region and represents the third association of Neandertal taxa to Initial Upper Palaeolithic lithic technocomplex in Western Europe. A detailed multidisciplinary approach, as presented here, is essential to advance understanding of Neandertal behavior, including funerary practices.},
}

@article {pmid33296644,
year = {2020},
author = {Jordan, B},
title = {[A poisoned gift].},
journal = {Medecine sciences : M/S},
volume = {36},
number = {12},
pages = {1233-1236},
doi = {10.1051/medsci/2020240},
pmid = {33296644},
issn = {1958-5381},
mesh = {Adaptor Proteins, Signal Transducing/genetics/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Animals ; COVID-19/epidemiology/*genetics/pathology/therapy ; Case-Control Studies ; Chromosomes, Human, Pair 3/*genetics ; Europe/epidemiology ; Evolution, Molecular ; *Genetic Loci ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Hominidae/genetics ; Humans ; Membrane Glycoproteins/genetics/metabolism ; Membrane Transport Proteins/genetics/metabolism ; Neanderthals/*genetics ; Pandemics ; Polymorphism, Single Nucleotide ; Protein Binding ; Receptors, CCR/genetics ; Receptors, CXCR6/genetics ; SARS-CoV-2/metabolism/*pathogenicity ; Severity of Illness Index ; },
abstract = {GWAS analysis of severe Covid patients implicates a major locus on chromosome 3. The corresponding 50 kb segment appears to originate from Neanderthal/Sapiens crossings, raising interesting evolutionary questions.},
}

Adaptor Proteins, Signal Transducing/genetics/metabolism
Angiotensin-Converting Enzyme 2/metabolism
Animals
COVID-19/epidemiology/*genetics/pathology/therapy
Case-Control Studies
Chromosomes, Human, Pair 3/*genetics
Europe/epidemiology
Evolution, Molecular
*Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Hominidae/genetics
Humans
Membrane Glycoproteins/genetics/metabolism
Membrane Transport Proteins/genetics/metabolism
Neanderthals/*genetics
Pandemics
Polymorphism, Single Nucleotide
Protein Binding
Receptors, CCR/genetics
Receptors, CXCR6/genetics
SARS-CoV-2/metabolism/*pathogenicity
Severity of Illness Index

@article {pmid33290582,
year = {2021},
author = {Brophy, JK and Moggi-Cecchi, J and Matthews, GJ and Bailey, SE},
title = {Comparative morphometric analyses of the deciduous molars of Homo naledi from the Dinaledi Chamber, South Africa.},
journal = {American journal of physical anthropology},
volume = {174},
number = {2},
pages = {299-314},
doi = {10.1002/ajpa.24190},
pmid = {33290582},
issn = {1096-8644},
mesh = {Animals ; Anthropology, Physical ; Fossils ; Hominidae/*anatomy & histology/*classification ; Humans ; Molar/*anatomy & histology ; Neanderthals/anatomy & histology/classification ; Odontometry ; Principal Component Analysis ; South Africa ; },
abstract = {OBJECTIVES: The purpose of this study is to help elucidate the taxonomic relationship between Homo naledi and other hominins.

MATERIALS AND METHODS: Homo naledi deciduous maxillary and mandibular molars from the Dinaledi Chamber, South Africa were compared to those of Australopithecus africanus, Australopithecus afarensis, Paranthropus robustus, Paranthropus boisei, early Homo sp., Homo erectus, early Homo sapiens, Upper Paleolithic H. sapiens, recent southern African H. sapiens, and Neanderthals by means of morphometric analyses of crown outlines and relative cusp areas. The crown shapes were analyzed using elliptical Fourier analyses followed by principal component analyses (PCA). The absolute and relative cusp areas were obtained in ImageJ and compared using PCA and cluster analyses.

RESULTS: PCA suggests that the crown shapes and relative cusp areas of mandibular molars are more diagnostic than the maxillary molars. The H. naledi deciduous mandibular first and second molar (dm1 and dm2) do not have a strong affinity to any taxon in the comparative sample in all analyses. While the H. naledi dm2 plots as an outlier in the relative cusp analysis, the H. naledi specimen fall closest to Australopithecus due to their relatively large metaconid, a primitive trait for the genus Homo. Although useful for differentiating Neanderthals from recent southern African H. sapiens and UP H. sapiens, the PCA of the relative cusp areas suggests that the deciduous maxillary second molars (dm2) do not differentiate other groups. The three H. naledi dm2 cuspal areas are variable and fall within the ranges of other Homo, as well as Australopithecus, and Paranthropus suggesting weak diagnostic utility.

DISCUSSION: This research provides another perspective on the morphology of, and variation within, H. naledi. The H. naledi deciduous molars do not consistently align with any genus or species in the comparative sample in either the crown shape or relative cusp analyses. This line of inquiry is consistent with other cranial and postcranial studies suggesting that H. naledi is unique.},
}

Animals
Anthropology, Physical
Fossils
Hominidae/*anatomy & histology/*classification
Humans
Molar/*anatomy & histology
Neanderthals/anatomy & histology/classification
Odontometry
Principal Component Analysis
South Africa

@article {pmid33278486,
year = {2021},
author = {Wendt, FR and Pathak, GA and Overstreet, C and Tylee, DS and Gelernter, J and Atkinson, EG and Polimanti, R},
title = {Characterizing the effect of background selection on the polygenicity of brain-related traits.},
journal = {Genomics},
volume = {113},
number = {1 Pt 1},
pages = {111-119},
pmid = {33278486},
issn = {1089-8646},
support = {F32 MH122058/MH/NIMH NIH HHS/United States ; R21 DA047527/DA/NIDA NIH HHS/United States ; R21 DC018098/DC/NIDCD NIH HHS/United States ; },
abstract = {BACKGROUND: Genome-wide association studies (GWAS) have demonstrated that psychopathology phenotypes are affected by many risk alleles with small effect (polygenicity). It is unclear how ubiquitously evolutionary pressures influence the genetic architecture of these traits.

METHODS: We partitioned SNP heritability to assess the contribution of background (BGS) and positive selection, Neanderthal local ancestry, functional significance, and genotype networks in 75 brain-related traits (8411 ≤ N ≤ 1,131,181, mean N = 205,289). We applied binary annotations by dichotomizing each measure based on top 2%, 1%, and 0.5% of all scores genome-wide. Effect size distribution features were calculated using GENESIS. We tested the relationship between effect size distribution descriptive statistics and natural selection. In a subset of traits, we explore the inclusion of diagnostic heterogeneity (e.g., number of diagnostic combinations and total symptoms) in the tested relationship.

RESULTS: SNP-heritability was enriched (false discovery rate q < 0.05) for loci with elevated BGS (7 phenotypes) and in genic (34 phenotypes) and loss-of-function (LoF)-intolerant regions (67 phenotypes). These effects were strongest in GWAS of schizophrenia (1.90-fold BGS, 1.16-fold genic, and 1.92-fold LoF), educational attainment (1.86-fold BGS, 1.12-fold genic, and 1.79-fold LoF), and cognitive performance (2.29-fold BGS, 1.12-fold genic, and 1.79-fold LoF). BGS (top 2%) significantly predicted effect size variance for trait-associated loci (σ2 parameter) in 75 brain-related traits (β = 4.39 × 10-5, p = 1.43 × 10-5, model r2 = 0.548). Considering the number of DSM-5 diagnostic combinations per psychiatric disorder improved model fit (σ2 ~ BTop2% × Genic × diagnostic combinations; model r2 = 0.661).

CONCLUSIONS: Brain-related phenotypes with larger variance in risk locus effect sizes are associated with loci under BGS. We show exploratory results suggesting that diagnostic complexity may also contribute to the increased polygenicity of psychiatric disorders.},
}

@article {pmid33264306,
year = {2020},
author = {Riga, A and Boggioni, M and Papini, A and Buzi, C and Profico, A and Di Vincenzo, F and Marchi, D and Moggi-Cecchi, J and Manzi, G},
title = {In situ observations on the dentition and oral cavity of the Neanderthal skeleton from Altamura (Italy).},
journal = {PloS one},
volume = {15},
number = {12},
pages = {e0241713},
pmid = {33264306},
issn = {1932-6203},
mesh = {Animals ; Caves ; *Dentition ; *Fossils ; Hominidae/*anatomy & histology ; Humans ; Italy ; Mandible/anatomy & histology ; Maxilla/anatomy & histology ; Mouth/physiology ; Neanderthals/*anatomy & histology ; Paleodontology ; Skull/anatomy & histology ; Tooth/anatomy & histology ; },
abstract = {The Neanderthal specimen from Lamalunga Cave, near Altamura (Apulia, Italy), was discovered during a speleological survey in 1993. The specimen is one of the most complete fossil hominins in Europe and its state of preservation is exceptional, although it is stuck in calcareous concretions and the bones are mostly covered by calcite depositions. Nevertheless, it is possible to carry out some observations on craniodental features that have not previously been described. In this work, we present an account of the oral cavity, made possible by the use of a videoscope, which allowed us to reach some hidden parts of the mandible and palate. This is the first detailed overview of the teeth and maxillary bones of the Neanderthal skeleton from Altamura. The dentition is almost complete. However, two teeth (upper right P3 and upper left M1) were lost ante mortem and four teeth (lower right I1 and P3 and lower left I1 and I2) were lost most probably post mortem. Dental wear is marked. The erupted M3s and the inversion of the compensating curve of Wilson in the M1s and M2s but not in the M3s suggest that the individual is fully adult, but not old. Although most of the teeth have their roots exposed for several millimeters, the periodontal bone appears to be in good condition overall, except in correspondence of the two ante-mortem tooth losses. X-rays of the anterior teeth show a periapical lesion, probably linked to the advanced dental wear. We also observed a weak expression of taurodontism in the posterior dentition and the presence of a retromolar space, features consistent with an attribution to the Neanderthal hypodigm; this attribution is also supported by aspects of the cranial morphology, the morphometric analysis of the scapula and preliminary mtDNA data. There is also a well-developed palatine torus, to the best of our knowledge a feature not previously described in Neanderthals.},
}

Animals
Caves
*Dentition
*Fossils
Hominidae/*anatomy & histology
Humans
Italy
Mandible/anatomy & histology
Maxilla/anatomy & histology
Mouth/physiology
Neanderthals/*anatomy & histology
Paleodontology
Skull/anatomy & histology
Tooth/anatomy & histology

@article {pmid33247712,
year = {2021},
author = {Dannemann, M},
title = {The Population-Specific Impact of Neandertal Introgression on Human Disease.},
journal = {Genome biology and evolution},
volume = {13},
number = {1},
pages = {},
doi = {10.1093/gbe/evaa250},
pmid = {33247712},
issn = {1759-6653},
abstract = {Since the discovery of admixture between modern humans and Neandertals, multiple studies investigated the effect of Neandertal-derived DNA on human disease and nondisease phenotypes. These studies have linked Neandertal ancestry to skin- and hair-related phenotypes, immunity, neurological, and behavioral traits. However, these inferences have so far been limited to cohorts with participants of European ancestry. Here, I analyze summary statistics from 40 disease GWAS (genome-wide association study) cohorts of ∼212,000 individuals provided by the Biobank Japan Project for phenotypic effects of Neandertal DNA. I show that Neandertal DNA is associated with autoimmune diseases, prostate cancer and type 2 diabetes. Many of these disease associations are linked to population-specific Neandertal DNA, highlighting the importance of studying a wider range of ancestries to characterize the phenotypic legacy of Neandertals in people today.},
}

@article {pmid33245148,
year = {2021},
author = {Mineta, K and Goto, K and Gojobori, T and Alkuraya, FS},
title = {Indigenous Arabs have an intermediate frequency of a Neanderthal-derived COVID-19 risk haplotype compared with other world populations.},
journal = {Clinical genetics},
volume = {99},
number = {3},
pages = {484-485},
doi = {10.1111/cge.13885},
pmid = {33245148},
issn = {1399-0004},
mesh = {Alleles ; Animals ; Arabs/*genetics ; COVID-19/*genetics/virology ; *Gene Frequency ; *Genetic Predisposition to Disease ; Haplotypes/*genetics ; Heterozygote ; Homozygote ; Humans ; Neanderthals/*genetics ; Polymorphism, Single Nucleotide/genetics ; Population Groups/*genetics ; Risk Factors ; SARS-CoV-2/physiology ; Saudi Arabia ; },
}

Alleles
Animals
Arabs/*genetics
COVID-19/*genetics/virology
*Gene Frequency
*Genetic Predisposition to Disease
Haplotypes/*genetics
Heterozygote
Homozygote
Humans
Neanderthals/*genetics
Polymorphism, Single Nucleotide/genetics
Population Groups/*genetics
Risk Factors
SARS-CoV-2/physiology
Saudi Arabia

@article {pmid33244047,
year = {2020},
author = {Bardo, A and Moncel, MH and Dunmore, CJ and Kivell, TL and Pouydebat, E and Cornette, R},
title = {The implications of thumb movements for Neanderthal and modern human manipulation.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {19323},
pmid = {33244047},
issn = {2045-2322},
support = {819960/ERC_/European Research Council/International ; },
mesh = {Adult ; Animals ; Anthropology, Physical ; Biological Evolution ; Female ; Fossils/anatomy & histology ; Hand Strength/physiology ; History, 21st Century ; History, Ancient ; Humans ; Imaging, Three-Dimensional ; Male ; Metacarpal Bones/anatomy & histology ; Models, Biological ; Movement ; Neanderthals/*anatomy & histology/*physiology ; Species Specificity ; Thumb/*anatomy & histology/*physiology ; Trapezium Bone/anatomy & histology ; },
abstract = {Much research has debated the technological abilities of Neanderthals relative to those of early modern humans, with a particular focus on subtle differences in thumb morphology and how this may reflect differences in manipulative behaviors in these two species. Here, we provide a novel perspective on this debate through a 3D geometric morphometric analysis of shape covariation between the trapezial and proximal first metacarpal articular surfaces of Neanderthals (Homo neanderthalensis) in comparison to early and recent humans (Homo sapiens). Results show a distinct pattern of shape covariation in Neanderthals, consistent with more extended and adducted thumb postures that may reflect habitual use of grips commonly used for hafted tools. Both Neanderthals and recent humans demonstrate high intraspecific variation in shape covariation. This intraspecific variation is likely the result of genetic and/or developmental differences, but may also reflect, in part, differing functional requirements imposed by the use of varied tool-kits. These results underscore the importance of holistic joint shape analysis for understanding the functional capabilities and evolution of the modern human thumb.},
}

Adult
Animals
Anthropology, Physical
Biological Evolution
Female
Fossils/anatomy & histology
Hand Strength/physiology
History, 21st Century
History, Ancient
Humans
Imaging, Three-Dimensional
Male
Metacarpal Bones/anatomy & histology
Models, Biological
Movement
Neanderthals/*anatomy & histology/*physiology
Species Specificity
Thumb/*anatomy & histology/*physiology
Trapezium Bone/anatomy & histology

@article {pmid33230523,
year = {2021},
author = {Aarts, JMMJG and Alink, GM and Franssen, HJ and Roebroeks, W},
title = {Evolution of Hominin Detoxification: Neanderthal and Modern Human Ah Receptor Respond Similarly to TCDD.},
journal = {Molecular biology and evolution},
volume = {38},
number = {4},
pages = {1292-1305},
doi = {10.1093/molbev/msaa287},
pmid = {33230523},
issn = {1537-1719},
abstract = {In studies of hominin adaptations to fire use, the role of the aryl hydrocarbon receptor (AHR) in the evolution of detoxification has been highlighted, including statements that the modern human AHR confers a significantly better capacity to deal with toxic smoke components than the Neanderthal AHR. To evaluate this, we compared the AHR-controlled induction of cytochrome P4501A1 (CYP1A1) mRNA in HeLa human cervix epithelial adenocarcinoma cells transfected with an Altai-Neanderthal or a modern human reference AHR expression construct, and exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We compared the complete AHR mRNA sequences including the untranslated regions (UTRs), maintaining the original codon usage. We observe no significant difference in CYP1A1 induction by TCDD between Neanderthal and modern human AHR, whereas a 150-1,000 times difference was previously reported in a study of the AHR coding region optimized for mammalian codon usage and expressed in rat cells. Our study exemplifies that expression in a homologous cellular background is of major importance to determine (ancient) protein activity. The Neanderthal and modern human dose-response curves almost coincide, except for a slightly higher extrapolated maximum for the Neanderthal AHR, possibly caused by a 5'-UTR G-variant known from modern humans (rs7796976). Our results are strongly at odds with a major role of the modern human AHR in the evolution of hominin detoxification of smoke components and consistent with our previous study based on 18 relevant genes in addition to AHR, which concluded that efficient detoxification alleles are more dominant in ancient hominins, chimpanzees, and gorillas than in modern humans.},
}

@article {pmid33226710,
year = {2021},
author = {Weyrich, LS},
title = {The evolutionary history of the human oral microbiota and its implications for modern health.},
journal = {Periodontology 2000},
volume = {85},
number = {1},
pages = {90-100},
doi = {10.1111/prd.12353},
pmid = {33226710},
issn = {1600-0757},
abstract = {Numerous biological and cultural factors influence the microbial communities (microbiota) that inhabit the human mouth, including diet, environment, hygiene, physiology, health status, genetics, and lifestyle. As oral microbiota can underpin oral and systemic diseases, tracing the evolutionary history of oral microbiota and the factors that shape its origins will unlock information to mitigate disease today. Despite this, the origins of many oral microbes remain unknown, and the key factors in the past that shaped our oral microbiota are only now emerging. High throughput DNA sequencing of oral microbiota using ancient DNA and comparative anthropological methodologies has been employed to investigate oral microbiota origins, revealing a complex, rich history. Here, I review the current literature on the factors that shaped and guided oral microbiota evolution, both in Europe and globally. In Europe, oral microbiota evolution was shaped by interactions with Neandertals, the adaptation of farming, widespread integration of industrialization, and postindustrial lifestyles that emerged after World War II. Globally, evidence for a multitude of different oral microbiota histories is emerging, likely supporting dissimilarities in modern oral health across discrete human populations. I highlight how these evolutionary changes are linked to the development of modern oral diseases and discuss the remaining factors that need to be addressed to improve this embryonic field of research. I argue that understanding the evolutionary history of our oral microbiota is necessary to identify new treatment and prevention options to improve oral and systemic health in the future.},
}

@article {pmid33218283,
year = {2021},
author = {Gregory, MD and Kippenhan, JS and Kohn, P and Eisenberg, DP and Callicott, JH and Kolachana, B and Berman, KF},
title = {Neanderthal-Derived Genetic Variation is Associated with Functional Connectivity in the Brains of Living Humans.},
journal = {Brain connectivity},
volume = {11},
number = {1},
pages = {38-44},
doi = {10.1089/brain.2020.0809},
pmid = {33218283},
issn = {2158-0022},
abstract = {Aim: To determine whether Neanderthal-derived genetic variation relates to functional connectivity patterns in the brains of living modern humans. Introduction: Nearly 50,000 years ago, Neanderthals interbred with ancestors of modern humans, imparting a genetic legacy that lives on today. The vestiges of this Neanderthal-derived genetic variation have been previously shown to be enriched in genes coding for neurogenesis and myelination and to alter skull shape and brain structure in living people. Materials and Methods: Using two independent cohorts totaling 553 healthy individuals, we employed multivariate distance matrix regression (MDMR) to determine whether any brain areas exhibited whole-brain functional connectivity patterns that significantly related to the degree of Neanderthal introgression. Identified clusters were then used as regions of interest in follow-up seed-based functional connectivity analyses to determine the connectivity patterns driving the relationships. Results: The MDMR analysis revealed that the percentage of Neanderthal-originating polymorphisms was significantly associated with the functional connectivity patterns of an area of the intraparietal sulcus (IPS) that was nearly identical in both cohorts. Using these IPS clusters as regions of interest in seed-based connectivity analyses, we found, again in both cohorts, that individuals with a higher proportion of Neanderthal-derived genetic variation showed increased IPS functional connectivity with visual processing regions, but decreased IPS connectivity with regions underlying social cognition. Conclusions: These findings demonstrate that the remnants of Neanderthal admixture continue to influence human brain function today, in ways that are consistent with anthropological conceptualizations of Neanderthal phenotypes, including the possibility that Neanderthals may have depended upon visual processing capabilities at the expense of social cognition, and this may have contributed to the extinction of this species through reduced cultural maintenance and inability to cope with fluctuating resources. This and other studies capitalizing on the emerging science surrounding ancient DNA provide a window through which to view an ancient lineage long past.},
}

@article {pmid33170414,
year = {2020},
author = {Madison, P},
title = {Characterized by Darkness: Reconsidering the Origins of the Brutish Neanderthal.},
journal = {Journal of the history of biology},
volume = {53},
number = {4},
pages = {493-519},
pmid = {33170414},
issn = {1573-0387},
support = {60669//John Templeton Foundation/International ; Center for Biology//School of Life Sciences, Arizona State University/International ; Society//School of Life Sciences, Arizona State University/International ; },
abstract = {The extinct human relatives known as Neanderthals (Homo neanderthalensis) have long been described as brutish and dumb. This conception is often traced to paleontologist Marcellin Boule (1861-1942), who published a detailed analysis on a Neanderthal skeleton in the early twentieth century. The conventional historical narrative claims that Boule made an error in his analysis, causing the Neanderthals to be considered brutish. This essay challenges the narrative of "Boule's error," arguing instead that the brutish Neanderthal concept originated much earlier in the history of Neanderthal research and was, in fact, an invention of the earliest analyses of the first specimen recognized as a Neanderthal in the mid-nineteenth century. I argue that temporally relocating this conception of Neanderthals allows for a better understanding of the interconnected nature of the study of fossil humans and the science of living human races during the nineteenth century. This new view of the brutish Neanderthal sheds light on the earliest phases of the science that became paleoanthropology, while examining the racial, cultural, and political attitudes about race and extinction that accompanied the science at that time. By inspecting the ways in which the Neanderthals' image was a product of a particular time and place, we gain a perspective that provides a new basis for thinking about the conceptions of hominin fossil species.},
}

@article {pmid33139541,
year = {2020},
author = {Nava, A and Lugli, F and Romandini, M and Badino, F and Evans, D and Helbling, AH and Oxilia, G and Arrighi, S and Bortolini, E and Delpiano, D and Duches, R and Figus, C and Livraghi, A and Marciani, G and Silvestrini, S and Cipriani, A and Giovanardi, T and Pini, R and Tuniz, C and Bernardini, F and Dori, I and Coppa, A and Cristiani, E and Dean, C and Bondioli, L and Peresani, M and Müller, W and Benazzi, S},
title = {Early life of Neanderthals.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {117},
number = {46},
pages = {28719-28726},
pmid = {33139541},
issn = {1091-6490},
mesh = {Animals ; Dental Enamel/chemistry/*growth & development ; Humans ; Infant ; Infant, Newborn ; Neanderthals/*growth & development ; *Weaning ; },
abstract = {The early onset of weaning in modern humans has been linked to the high nutritional demand of brain development that is intimately connected with infant physiology and growth rate. In Neanderthals, ontogenetic patterns in early life are still debated, with some studies suggesting an accelerated development and others indicating only subtle differences vs. modern humans. Here we report the onset of weaning and rates of enamel growth using an unprecedented sample set of three late (∼70 to 50 ka) Neanderthals and one Upper Paleolithic modern human from northeastern Italy via spatially resolved chemical/isotopic analyses and histomorphometry of deciduous teeth. Our results reveal that the modern human nursing strategy, with onset of weaning at 5 to 6 mo, was present among these Neanderthals. This evidence, combined with dental development akin to modern humans, highlights their similar metabolic constraints during early life and excludes late weaning as a factor contributing to Neanderthals' demise.},
}

Animals
Dental Enamel/chemistry/*growth & development
Humans
Infant
Infant, Newborn
Neanderthals/*growth & development
*Weaning

@article {pmid33137550,
year = {2020},
author = {Palancar, CA and Torres-Tamayo, N and García-Martínez, D and García-Tabernero, A and Rosas, A and Bastir, M},
title = {Comparative anatomy and 3D geometric morphometrics of the El Sidrón atlases (C1).},
journal = {Journal of human evolution},
volume = {149},
number = {},
pages = {102897},
doi = {10.1016/j.jhevol.2020.102897},
pmid = {33137550},
issn = {1095-8606},
abstract = {The first cervical vertebra (atlas, C1) is an important element of the vertebral column because it connects the cranial base with the cervical column, thus helping to maintain head posture and contributing to neck mobility. However, few atlases are preserved in the fossil record because of the fragility of this vertebra. Consequently, only eight well-preserved atlases from adult Neandertals have been recovered and described. Here, we present nine new atlas remains from the El Sidrón Neandertal site (Asturias, Spain), two of which (SD-1643 and SD-1605/1595) are sufficiently well preserved to allow for a detailed comparative and three-dimensional geometric morphometric analysis. We compared standard linear measurements of SD-1643 and SD-1605/1595 with those of other Neandertal atlases and carried out three-dimensional geometric morphometric analyses to compare size and shape of SD-1643 and SD-1605/1595 with those of 28 Pan (Pan troglodytes and Pan paniscus), a broad comparative sample of 55 anatomically modern humans from African and European populations, and other fossil hominins (Neandertals, Homo antecessor, Paranthropus boisei). The El Sidrón atlas fossils show typical features of the Neandertal atlas morphology, such as caudal projection of the anterior tubercle, gracility of both the posterior tubercle and the tuberosity for the insertion of the transverse ligament, and an anteroposteriorly elongated neural canal. Furthermore, when compared with atlases from the other taxa, Neandertals exhibit species-specific features of atlas morphology including a relatively lower lateral mass height, relatively narrower transverse foramina, and flatter and more horizontally oriented articular facets. Some of these features fit with previous suggestions of shorter overall length of the cervical spine and potential differences in craniocervical posture and mobility. Our results may support a different spinopelvic alignment in this species, as the atlas morphology suggests reduced cervical lordosis.},
}

@article {pmid33130632,
year = {2020},
author = {Bruner, E and Lombard, M},
title = {The skull from Florisbad: a paleoneurological report.},
journal = {Journal of anthropological sciences = Rivista di antropologia : JASS},
volume = {98},
number = {},
pages = {},
doi = {10.4436/JASS.98014},
pmid = {33130632},
issn = {2037-0644},
mesh = {Animals ; Biological Evolution ; Cephalometry ; *Fossils ; Hominidae/*anatomy & histology ; Humans ; Neanderthals/anatomy & histology ; Paleontology ; Skull/*anatomy & histology ; South Africa ; },
abstract = {The Florisbad fossil cranium was found in South Africa in 1932. Different authors proposed a taxonomic affinity with early Homo sapiens, Neandertals or late Homo heidelbergensis. Here, we review its neurocranial morphology, to supply an updated perspective on its paleoneurological features. The curvature of the frontal squama is definitely within modern human variation, although the anterior cranial fossa is very broad, comparable to that of the Neandertals. In contrast, the parietal lobe and the vascular networks are more similar to the morphology observed in more archaic human species, such as Homo heidelbergensis. The endocranial anatomy of the Florisbad skull displays a mosaic of derived and plesiomorphic features, which makes this fossil compatible with distinct phylogenetic scenarios. None of these traits are, however, strictly diagnostic in terms of taxonomy. This specimen is central to the question on the possible anagenetic evolution from Homo heidelbergensis sensu lato to modern humans.},
}

Animals
Biological Evolution
Cephalometry
*Fossils
Hominidae/*anatomy & histology
Humans
Neanderthals/anatomy & histology
Paleontology
Skull/*anatomy & histology
South Africa

@article {pmid33122381,
year = {2020},
author = {Zhang, D and Xia, H and Chen, F and Li, B and Slon, V and Cheng, T and Yang, R and Jacobs, Z and Dai, Q and Massilani, D and Shen, X and Wang, J and Feng, X and Cao, P and Yang, MA and Yao, J and Yang, J and Madsen, DB and Han, Y and Ping, W and Liu, F and Perreault, C and Chen, X and Meyer, M and Kelso, J and Pääbo, S and Fu, Q},
title = {Denisovan DNA in Late Pleistocene sediments from Baishiya Karst Cave on the Tibetan Plateau.},
journal = {Science (New York, N.Y.)},
volume = {370},
number = {6516},
pages = {584-587},
doi = {10.1126/science.abb6320},
pmid = {33122381},
issn = {1095-9203},
mesh = {Animals ; *Caves ; DNA, Ancient/*isolation & purification ; DNA, Mitochondrial/genetics ; Geologic Sediments/*chemistry ; Hominidae/*classification/*genetics ; Humans ; Phylogeny ; Tibet ; },
abstract = {A late Middle Pleistocene mandible from Baishiya Karst Cave (BKC) on the Tibetan Plateau has been inferred to be from a Denisovan, an Asian hominin related to Neanderthals, on the basis of an amino acid substitution in its collagen. Here we describe the stratigraphy, chronology, and mitochondrial DNA extracted from the sediments in BKC. We recover Denisovan mitochondrial DNA from sediments deposited ~100 thousand and ~60 thousand years ago (ka) and possibly as recently as ~45 ka. The long-term occupation of BKC by Denisovans suggests that they may have adapted to life at high altitudes and may have contributed such adaptations to modern humans on the Tibetan Plateau.},
}

Animals
*Caves
DNA, Ancient/*isolation & purification
DNA, Mitochondrial/genetics
Geologic Sediments/*chemistry
Hominidae/*classification/*genetics
Humans
Phylogeny
Tibet

@article {pmid33111974,
year = {2021},
author = {Cofran, Z and Boone, M and Petticord, M},
title = {Virtually estimated endocranial volumes of the Krapina Neandertals.},
journal = {American journal of physical anthropology},
volume = {174},
number = {1},
pages = {117-128},
doi = {10.1002/ajpa.24165},
pmid = {33111974},
issn = {1096-8644},
mesh = {Animals ; Anthropology, Physical ; Cephalometry/*methods ; Female ; Fossils ; Hominidae/anatomy & histology ; Humans ; Imaging, Three-Dimensional ; Male ; Neanderthals/*anatomy & histology ; Skull/*anatomy & histology/*diagnostic imaging ; },
abstract = {OBJECTIVES: The Krapina rock shelter has yielded a large assemblage of early Neandertals. Although endocranial volume (ECV) has been estimated for four individuals from the site, several published values that appear in the literature warrant revisiting.

MATERIALS AND METHODS: We used virtual methods, including high-resolution surface models of fossils and 3D geometric morphometrics, to reconstruct endocasts and estimate ECV for five Krapina crania. We generated 10 reconstructions of each endocast to quantify missing data uncertainty. To assess the method and our ECV estimates, we applied these techniques to the Spy II Neandertal, and estimated ECV of a human reference endocast simulating the missing data of the Krapina fossils.

RESULTS: We obtained an average ECV estimate of 1,526 cm3 for Spy II, consistent with previous research. Estimated ECV of juveniles Krapina 1 and 2 average 1,419 and 1,286 cm3 , respectively. Estimates for the relatively complete adults Krapina 3 and 6 range from 1,247 to 1,310 cm3 and 1,135 to 1,207 cm3 , respectively, while the more fragmentary Krapina 5 averaged 1,397 cm3 . The missing data simulation suggests more fragmentary crania yield more uncertain and possibly overestimated ECVs.

CONCLUSIONS: We have provided new estimates of brain size of the Krapina Neandertals, including the first estimates for Krapina 2. Brain size at Krapina was similar to other pre-Würm Neandertals, within the range of but lower than the average of later Neandertals. Although the virtual approach overcomes many challenges of fossil preservation, our results are nevertheless subject to future revision.},
}

Animals
Anthropology, Physical
Cephalometry/*methods
Female
Fossils
Hominidae/anatomy & histology
Humans
Imaging, Three-Dimensional
Male
Neanderthals/*anatomy & histology
Skull/*anatomy & histology/*diagnostic imaging

@article {pmid33106620,
year = {2020},
author = {Luo, Y},
title = {Neanderthal DNA highlights complexity of COVID risk factors.},
journal = {Nature},
volume = {587},
number = {7835},
pages = {552-553},
pmid = {33106620},
issn = {1476-4687},
mesh = {Betacoronavirus ; COVID-19 ; *Coronavirus Infections/epidemiology ; DNA ; Humans ; *Neanderthals/genetics ; *Pandemics ; *Pneumonia, Viral ; Risk Factors ; SARS-CoV-2 ; },
}

Betacoronavirus
COVID-19
*Coronavirus Infections/epidemiology
DNA
Humans
*Neanderthals/genetics
*Pandemics
*Pneumonia, Viral
Risk Factors
SARS-CoV-2

@article {pmid33077870,
year = {2021},
author = {Yang, S and Varghese, AM and Sood, N and Chiattone, C and Akinola, NO and Huang, X and Gale, RP},
title = {Ethnic and geographic diversity of chronic lymphocytic leukaemia.},
journal = {Leukemia},
volume = {35},
number = {2},
pages = {433-439},
pmid = {33077870},
issn = {1476-5551},
mesh = {Aged ; Asian Americans/genetics/statistics & numerical data ; Ethnic Groups/*genetics/*statistics & numerical data ; European Continental Ancestry Group/genetics/statistics & numerical data ; Far East/epidemiology ; Female ; *Genetic Predisposition to Disease ; *Genetic Variation ; *Genetics, Population ; Genome, Human ; Geography ; Global Health ; Humans ; Incidence ; Leukemia, Lymphocytic, Chronic, B-Cell/*epidemiology/genetics/pathology ; Male ; Middle Aged ; Risk Factors ; },
abstract = {East Asians, Asian Indians and Amerindians have a five to ten-fold lower age-adjusted incidence rate (AAIR) of chronic lymphocytic leukaemia (CLL) compared with persons of predominately European descent. The data we review suggest a genetic rather than environmental basis for this discordance. All these populations arose from a common African Black ancestor but different clades have different admixture with archaic hominins including Neanderthals, Denisovans and Homo erectus, which may explain different CLL incidences. There are also some differences in clinical laboratory and molecular co-variates of CLL between these populations. Because the true age-adjusted incidence rate in African Blacks is unknown it is not possible to determine whether modern Europeans acquired susceptibility to CLL or the other populations lost susceptibility and/or developed resistance to developing CLL. We also found other B-cell lymphomas and T- and NK-cell cancers had different incidences in the populations we studied. These data provide clues to determining the cause(s) of CLL.},
}

Aged
Asian Americans/genetics/statistics & numerical data
Ethnic Groups/*genetics/*statistics & numerical data
European Continental Ancestry Group/genetics/statistics & numerical data
Far East/epidemiology
Female
*Genetic Predisposition to Disease
*Genetic Variation
*Genetics, Population
Genome, Human
Geography
Global Health
Humans
Incidence
Leukemia, Lymphocytic, Chronic, B-Cell/*epidemiology/genetics/pathology
Male
Middle Aged
Risk Factors

@article {pmid33043635,
year = {2020},
author = {},
title = {Risk Variant for Severe COVID-19 Inherited from Neanderthals.},
journal = {American journal of medical genetics. Part A},
volume = {182},
number = {10},
pages = {2203-2204},
doi = {10.1002/ajmg.a.61247},
pmid = {33043635},
issn = {1552-4833},
mesh = {Animals ; Betacoronavirus/*genetics ; COVID-19 ; Coronavirus Infections/epidemiology/*virology ; Female ; Haplotypes ; Humans ; Male ; Neanderthals ; *Pandemics ; Pneumonia, Viral/epidemiology/*virology ; Risk Factors ; SARS-CoV-2 ; Sex Factors ; },
}

Animals
Betacoronavirus/*genetics
COVID-19
Coronavirus Infections/epidemiology/*virology
Female
Haplotypes
Humans
Male
Neanderthals
*Pandemics
Pneumonia, Viral/epidemiology/*virology
Risk Factors
SARS-CoV-2
Sex Factors

@article {pmid33039881,
year = {2020},
author = {Pan, L and Dumoncel, J and Mazurier, A and Zanolli, C},
title = {Hominin diversity in East Asia during the Middle Pleistocene: A premolar endostructural perspective.},
journal = {Journal of human evolution},
volume = {148},
number = {},
pages = {102888},
doi = {10.1016/j.jhevol.2020.102888},
pmid = {33039881},
issn = {1095-8606},
abstract = {Following the recent studies of East Asian mid-Middle to early Late Pleistocene hominin material, a large spectrum of morphological diversity has been recognized and the coexistence of archaic ('Homo erectus-like') and derived ('modern-like') dental morphological patterns has been highlighted. In fact, for most of these Chinese fossils, generally categorized as 'archaic Homo sapiens' or 'post-H. erectus Homo', the taxonomic attribution is a matter of contention. With the help of μCT techniques and a deformation-based 3D geometric morphometric approach, we focused on the morphological variation in the enamel-dentine junction (EDJ) of 18 upper and lower premolars from Chinese Middle Pleistocene hominins. We then compared our results with a number of fossil and modern human groups, including Early Pleistocene H. erectus from Sangiran; late Early Pleistocene hominins from Tighenif, Algeria; classic Neanderthals; and modern humans. Our results highlight an evolutionary/chronological trend of crown base reduction, elevation of EDJ topography, and EDJ surface simplification in the hominin groups studied here. Moreover, this study brings insights to the taxonomy/phylogeny of 6 late Middle Pleistocene specimens whose evolutionary placement has been debated for decades. Among these specimens, Changyang premolars show features that can be aligned with the Asian H. erectus hypodigm, whereas Panxian Dadong and Tongzi premolars are more similar to Late Pleistocene Homo. Compared with early to mid-Middle Pleistocene hominins in East Asia, late Middle Pleistocene hominins evince an enlarged morphological variation. A persistence of archaic morphotypes and possible admixture among populations during the late Middle Pleistocene are discussed.},
}

@article {pmid33028520,
year = {2020},
author = {García-Martínez, D and Bastir, M and Gómez-Olivencia, A and Maureille, B and Golovanova, L and Doronichev, V and Akazawa, T and Kondo, O and Ishida, H and Gascho, D and Zollikofer, CPE and de León, MP and Heuzé, Y},
title = {Early development of the Neanderthal ribcage reveals a different body shape at birth compared to modern humans.},
journal = {Science advances},
volume = {6},
number = {41},
pages = {},
pmid = {33028520},
issn = {2375-2548},
abstract = {Ontogenetic studies provide clues for understanding important paleobiological aspects of extinct species. When compared to that of modern humans, the adult Neanderthal thorax was shorter, deeper, and wider. This is related to the wide Neanderthal body and is consistent with their hypothetical large requirements for energy and oxygen. Whether these differences were already established at birth or appeared later during development is unknown. To delve into this question, we use virtual reconstruction tools and geometric morphometrics to recover the 3D morphology of the ribcages of four Neanderthal individuals from birth to around 3 years old: Mezmaiskaya 1, Le Moustier 2, Dederiyeh 1, and Roc de Marsal. Our results indicate that the comparatively deep and short ribcage of the Neanderthals was already present at birth, as were other skeletal species-specific traits. This morphology possibly represents the plesiomorphic condition shared with Homo erectus, and it is likely linked to large energetic requirements.},
}

@article {pmid32998156,
year = {2020},
author = {Zeberg, H and Pääbo, S},
title = {The major genetic risk factor for severe COVID-19 is inherited from Neanderthals.},
journal = {Nature},
volume = {587},
number = {7835},
pages = {610-612},
pmid = {32998156},
issn = {1476-4687},
mesh = {Animals ; Asia/ethnology ; COVID-19/complications/*genetics/*physiopathology ; Case-Control Studies ; Chromosomes, Human, Pair 3/genetics ; Europe/ethnology ; *Genetic Predisposition to Disease ; Genetic Variation/genetics ; Genome-Wide Association Study ; Haplotypes/genetics ; Hospitalization ; Humans ; Linkage Disequilibrium/genetics ; Multigene Family/genetics ; Neanderthals/*genetics ; Phylogeny ; Severe Acute Respiratory Syndrome/complications/genetics/physiopathology ; },
abstract = {A recent genetic association study1 identified a gene cluster on chromosome 3 as a risk locus for respiratory failure after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A separate study (COVID-19 Host Genetics Initiative)2 comprising 3,199 hospitalized patients with coronavirus disease 2019 (COVID-19) and control individuals showed that this cluster is the major genetic risk factor for severe symptoms after SARS-CoV-2 infection and hospitalization. Here we show that the risk is conferred by a genomic segment of around 50 kilobases in size that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe.},
}

Animals
Asia/ethnology
COVID-19/complications/*genetics/*physiopathology
Case-Control Studies
Chromosomes, Human, Pair 3/genetics
Europe/ethnology
*Genetic Predisposition to Disease
Genetic Variation/genetics
Genome-Wide Association Study
Haplotypes/genetics
Hospitalization
Humans
Linkage Disequilibrium/genetics
Multigene Family/genetics
Neanderthals/*genetics
Phylogeny
Severe Acute Respiratory Syndrome/complications/genetics/physiopathology

@article {pmid32989161,
year = {2020},
author = {Haws, JA and Benedetti, MM and Talamo, S and Bicho, N and Cascalheira, J and Ellis, MG and Carvalho, MM and Friedl, L and Pereira, T and Zinsious, BK},
title = {The early Aurignacian dispersal of modern humans into westernmost Eurasia.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {117},
number = {41},
pages = {25414-25422},
pmid = {32989161},
issn = {1091-6490},
mesh = {*Archaeology ; *Demography ; Emigration and Immigration/history ; *Fossils ; History, Ancient ; Humans ; Portugal ; Radiometric Dating ; },
abstract = {Documenting the first appearance of modern humans in a given region is key to understanding the dispersal process and the replacement or assimilation of indigenous human populations such as the Neanderthals. The Iberian Peninsula was the last refuge of Neanderthal populations as modern humans advanced across Eurasia. Here we present evidence of an early Aurignacian occupation at Lapa do Picareiro in central Portugal. Diagnostic artifacts were found in a sealed stratigraphic layer dated 41.1 to 38.1 ka cal BP, documenting a modern human presence on the western margin of Iberia ∼5,000 years earlier than previously known. The data indicate a rapid modern human dispersal across southern Europe, reaching the westernmost edge where Neanderthals were thought to persist. The results support the notion of a mosaic process of modern human dispersal and replacement of indigenous Neanderthal populations.},
}

*Archaeology
*Demography
Emigration and Immigration/history
*Fossils
History, Ancient
Humans
Portugal
Radiometric Dating

@article {pmid32975051,
year = {2021},
author = {Chirchir, H},
title = {Trabecular bone in domestic dogs and wolves: Implications for understanding human self-domestication.},
journal = {Anatomical record (Hoboken, N.J. : 2007)},
volume = {304},
number = {1},
pages = {31-41},
doi = {10.1002/ar.24510},
pmid = {32975051},
issn = {1932-8494},
mesh = {Animals ; Behavior, Animal/physiology ; Cancellous Bone/*anatomy & histology/diagnostic imaging ; Dogs ; *Domestication ; Femur Head/*anatomy & histology/diagnostic imaging ; Tibia/*anatomy & histology/diagnostic imaging ; Wolves ; X-Ray Microtomography ; },
abstract = {The process of domestication is complex and results in significant morphological, cognitive, and physiological changes. In canids, some of the traits indicative of domestication of domestic dogs compared to their wild counterparts the wolves are prosociality toward humans, reduced stress hormone levels, and reduced cranial capacity. Research suggests that selection for prosociality among dogs resulted in morphological changes such as reduction in cranial capacity, juvenilization of the face, and overall gracile morphology. Interestingly, similar features have been described in modern humans compared to extinct species of Homo, for example, Neanderthals. Therefore, the human self-domestication hypothesis has been proposed to partially explain the gracile modern human skeleton. Specifically, that as modern humans settled in communities, there was increased selection for prosociality (intergroup cooperation); and one of the by-products of this selection was the evolution of a gracile skeleton, including a slight reduction in cranial capacity, reduced brow ridge and tooth size, and low trabecular bone fraction (TBF). However, TBF variation has not been tested between domestic dogs and wolves, who underwent self-domestication. Thus, this study tests the hypothesis that dogs have low TBF as a consequence of domestication compared to their wild counterparts, the wolves, by comparing TBF in the hindlimbs-proximal femur and distal tibia- of the two species. Wilcoxon rank sum tests show that dogs have lower TBF values than wolves in both elements. These preliminary results add to the literature documenting changes in self-domesticated species and provide a potential analog to further the understanding of self-domestication.},
}

Animals
Behavior, Animal/physiology
Cancellous Bone/*anatomy & histology/diagnostic imaging
Dogs
*Domestication
Femur Head/*anatomy & histology/diagnostic imaging
Tibia/*anatomy & histology/diagnostic imaging
Wolves
X-Ray Microtomography

@article {pmid32973032,
year = {2020},
author = {Petr, M and Hajdinjak, M and Fu, Q and Essel, E and Rougier, H and Crevecoeur, I and Semal, P and Golovanova, LV and Doronichev, VB and Lalueza-Fox, C and de la Rasilla, M and Rosas, A and Shunkov, MV and Kozlikin, MB and Derevianko, AP and Vernot, B and Meyer, M and Kelso, J},
title = {The evolutionary history of Neanderthal and Denisovan Y chromosomes.},
journal = {Science (New York, N.Y.)},
volume = {369},
number = {6511},
pages = {1653-1656},
doi = {10.1126/science.abb6460},
pmid = {32973032},
issn = {1095-9203},
support = {/ERC_/European Research Council/International ; },
mesh = {Animals ; Chromosomes, Human, Y/genetics ; DNA, Ancient ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Humans ; *Life History Traits ; Male ; Neanderthals/classification/*genetics ; Phylogeny ; Y Chromosome/*genetics ; },
abstract = {Ancient DNA has provided new insights into many aspects of human history. However, we lack comprehensive studies of the Y chromosomes of Denisovans and Neanderthals because the majority of specimens that have been sequenced to sufficient coverage are female. Sequencing Y chromosomes from two Denisovans and three Neanderthals shows that the Y chromosomes of Denisovans split around 700 thousand years ago from a lineage shared by Neanderthals and modern human Y chromosomes, which diverged from each other around 370 thousand years ago. The phylogenetic relationships of archaic and modern human Y chromosomes differ from the population relationships inferred from the autosomal genomes and mirror mitochondrial DNA phylogenies, indicating replacement of both the mitochondrial and Y chromosomal gene pools in late Neanderthals. This replacement is plausible if the low effective population size of Neanderthals resulted in an increased genetic load in Neanderthals relative to modern humans.},
}

Animals
Chromosomes, Human, Y/genetics
DNA, Ancient
DNA, Mitochondrial/genetics
*Evolution, Molecular
Humans
*Life History Traits
Male
Neanderthals/classification/*genetics
Phylogeny
Y Chromosome/*genetics

@article {pmid32973019,
year = {2020},
author = {Schierup, MH},
title = {The last pieces of a puzzling early meeting.},
journal = {Science (New York, N.Y.)},
volume = {369},
number = {6511},
pages = {1565-1566},
doi = {10.1126/science.abe2766},
pmid = {32973019},
issn = {1095-9203},
mesh = {Animals ; Biological Evolution ; *Neanderthals ; Y Chromosome ; },
}

Animals
Biological Evolution
*Neanderthals
Y Chromosome

@article {pmid32964411,
year = {2020},
author = {Wei, P and Lu, H and Carlson, KJ and Zhang, H and Hui, J and Zhu, M and He, K and Jashashvili, T and Zhang, X and Yuan, H and Xing, S},
title = {The upper limb skeleton and behavioral lateralization of modern humans from Zhaoguo Cave, southwestern China.},
journal = {American journal of physical anthropology},
volume = {173},
number = {4},
pages = {671-696},
doi = {10.1002/ajpa.24147},
pmid = {32964411},
issn = {1096-8644},
mesh = {Adaptation, Physiological/*physiology ; Adult ; Animals ; Burial/history ; Caves ; China/ethnology ; Female ; Fossils ; History, Ancient ; Humans ; Humerus/*anatomy & histology/*pathology ; Male ; Neanderthals ; },
abstract = {OBJECTIVES: Aims of the study are to initially describe and comparatively evaluate the morphology of the new Zhaoguo M1 upper limb remains, and contextualize upper limb functional adaptations among those of other worldwide Upper Paleolithic (UP) humans to make inferences about subsistence-related activity patterns in southwestern China at the Pleistocene-Holocene boundary.

MATERIALS AND METHODS: The preserved Zhaoguo M1 skeletal remains include paired humeri, ulnae, and radii, among others. These specimens were scanned using micro-computed tomography to evaluate internal structural properties, while external osteometric dimensions of the Zhaoguo M1 upper limb elements also were acquired. Both sets of measurements were compared to published data on Neandertals, and Middle and Upper Paleolithic modern humans.

RESULTS: The upper limb elements of Zhaoguo M1 display a suite of characteristics that generally resemble those of other contemporary Late UP (LUP) modern humans, while robusticity indices generally fall within the upper range of LUP variation. The Zhaoguo M1 upper limb elements display fewer traits resembling those of late archaic humans. The Zhaoguo M1 individual exhibits diaphyseal asymmetry in several upper limb elements suggesting left hand dominance. When evaluating the full range of magnitudes of humeral bilateral asymmetry in the comparative sample, Zhaoguo M1 falls at the lower end overall, but yet is relatively higher than contemporary LUP modern humans specifically from East Eurasia.

DISCUSSION: The Zhaoguo M1 individual suggests typical LUP modern human upper limb morphology persisted in southwest China until the end of the last glacial period. Upper limb bone asymmetry of Zhaoguo M1 also indicates that behavioral activities attributed to a hunter-gatherer tradition apparently extended through the Pleistocene-Holocene transition in this region.},
}

Adaptation, Physiological/*physiology
Adult
Animals
Burial/history
Caves
China/ethnology
Female
Fossils
History, Ancient
Humans
Humerus/*anatomy & histology/*pathology
Male
Neanderthals

@article {pmid32963029,
year = {2020},
author = {Bokelmann, L and Glocke, I and Meyer, M},
title = {Reconstructing double-stranded DNA fragments on a single-molecule level reveals patterns of degradation in ancient samples.},
journal = {Genome research},
volume = {30},
number = {10},
pages = {1449-1457},
pmid = {32963029},
issn = {1549-5469},
abstract = {Extensive manipulations involved in the preparation of DNA samples for sequencing have hitherto made it impossible to determine the precise structure of double-stranded DNA fragments being sequenced, such as the presence of blunt ends, single-stranded overhangs, or single-strand breaks. We here describe MatchSeq, a method that combines single-stranded DNA library preparation from diluted DNA samples with computational sequence matching, allowing the reconstruction of double-stranded DNA fragments on a single-molecule level. The application of MatchSeq to Neanderthal DNA, a particularly complex source of degraded DNA, reveals that 1- or 2-nt overhangs and blunt ends dominate the ends of ancient DNA molecules and that short gaps exist, which are predominantly caused by the loss of individual purines. We further show that deamination of cytosine to uracil occurs in both single- and double-stranded contexts close to the ends of molecules, and that single-stranded parts of DNA fragments are enriched in pyrimidines. MatchSeq provides unprecedented resolution for interrogating the structures of fragmented double-stranded DNA and can be applied to fragmented double-stranded DNA isolated from any biological source. The method relies on well-established laboratory techniques and can easily be integrated into routine data generation. This possibility is shown by the successful reconstruction of double-stranded DNA fragments from previously published single-stranded sequence data, allowing a more comprehensive characterization of the biochemical properties not only of ancient DNA but also of cell-free DNA from human blood plasma, a clinically relevant marker for the diagnosis and monitoring of disease.},
}

@article {pmid32927399,
year = {2020},
author = {Bailey, SE and Sorrentino, R and Mancuso, G and Hublin, JJ and Benazzi, S},
title = {Taxonomic differences in deciduous lower first molar crown outlines of Homo sapiens and Homo neanderthalensis.},
journal = {Journal of human evolution},
volume = {147},
number = {},
pages = {102864},
doi = {10.1016/j.jhevol.2020.102864},
pmid = {32927399},
issn = {1095-8606},
abstract = {Recent studies have demonstrated that the outline shapes of deciduous upper and lower second molars and the deciduous upper first molar are useful for diagnosing hominin taxa-especially Homo neanderthalensis and Homo sapiens. Building on these studies, we use geometric morphometric methods to assess the taxonomic significance of the crown outline of the lower first deciduous molar (dm1). We test whether the crown shape of the dm1 distinguishes H. neanderthalensis from H. sapiens and explore whether dm1 crown shape can be used to accurately assign individuals to taxa. Our fossil sample includes 3 early H. sapiens, 7 Upper Paleolithic H. sapiens, and 13 H. neanderthalensis individuals. Our recent human sample includes 103 individuals from Africa, Australia, Europe, South America, and South Asia. Our results indicate that H. neanderthalensis dm1s cluster fairly tightly and separate well from those of Upper Paleolithic H. sapiens. However, we also found that the range of shapes in the recent human sample completely overlaps the ranges of all fossil samples. Consequently, results of the quadratic discriminant analysis based on the first 8 principal components (PCs) representing more than 90% of the variation were mixed. Lower dm1s were correctly classified in 87.3% of the individuals; the combined H. sapiens sample had greater success (90.2%) in assigning individuals than did the H. neanderthalensis sample (61.5%). When the analysis was run removing the highly variable recent human sample, accuracy increased to 84.6% for H. neanderthalensis, and 57.1% of Upper Paleolithic H. sapiens were classified correctly by using the first 4 PCs (70.3%). We conclude that caution is warranted when assigning isolated dm1 crowns to taxa; while an assignment to H. neanderthalensis has a high probability of being correct, assignment to Upper Paleolithic H. sapiens is less certain.},
}

@article {pmid32918796,
year = {2021},
author = {Breyl, M},
title = {Triangulating Neanderthal cognition: A tale of not seeing the forest for the trees.},
journal = {Wiley interdisciplinary reviews. Cognitive science},
volume = {12},
number = {2},
pages = {e1545},
doi = {10.1002/wcs.1545},
pmid = {32918796},
issn = {1939-5086},
abstract = {The inference of Neanderthal cognition, including their cultural and linguistic capabilities, has persisted as a fiercely debated research topic for decades. This lack of consensus is substantially based on inherent uncertainties in reconstructing prehistory out of indirect evidence as well as other methodological limitations. Further factors include systemic difficulties within interdisciplinary discourse, data artifacts, historic research biases, and the sheer scope of the relevant research. Given the degrees of freedom in interpretation ensuing from these complications, any attempt to find approximate answers to the yet unsettled pertinent discourse may not rest on single studies, but instead a careful and comprehensive interdisciplinary synthesis of findings. Triangulating Neanderthals' cognition by considering the plethora of data, diverse perspectives and aforementioned complexities present within the literature constitutes the currently most reliable pathway to tentative conclusions. While some uncertainties remain, such an approach paints the picture of an extensive shared humanity between anatomically modern humans and Neanderthals. This article is categorized under: Cognitive Biology > Evolutionary Roots of Cognition Linguistics > Evolution of Language.},
}

@article {pmid32914870,
year = {2021},
author = {Oxilia, G and Bortolini, E and Badino, F and Bernardini, F and Gazzoni, V and Lugli, F and Romandini, M and Radini, A and Terlato, G and Marciani, G and Silvestrini, S and Menghi Sartorio, JC and Thun Hohenstein, U and Fiorenza, L and Kullmer, O and Tuniz, C and Moggi Cecchi, J and Talamo, S and Fontana, F and Peresani, M and Benazzi, S and Cristiani, E},
title = {Exploring late Paleolithic and Mesolithic diet in the Eastern Alpine region of Italy through multiple proxies.},
journal = {American journal of physical anthropology},
volume = {174},
number = {2},
pages = {232-253},
pmid = {32914870},
issn = {1096-8644},
mesh = {Animals ; Carbon Isotopes/analysis ; Dental Calculus/chemistry ; Diet/*history ; Feeding Behavior/*physiology ; History, Ancient ; Humans ; Italy ; Molar/pathology ; Neanderthals ; Paleontology ; Tooth Wear/pathology ; },
abstract = {OBJECTIVES: The analysis of prehistoric human dietary habits is key for understanding the effects of paleoenvironmental changes on the evolution of cultural and social human behaviors. In this study, we compare results from zooarchaeological, stable isotope and dental calculus analyses as well as lower second molar macrowear patterns to gain a broader understanding of the diet of three individuals who lived between the end of the Late Pleistocene and the Early Holocene (ca., 17-8 ky cal BP) in the Eastern Alpine region of Italy.

MATERIALS AND METHODS: We analyze individuals buried at the sites of Riparo Tagliente (Verona), Riparo Villabruna, and Mondeval de Sora (Belluno). The three burials provide a unique dataset for diachronically exploring the influence of climatic changes on human subsistence strategies.

RESULTS: Isotopic results indicate that all individuals likely relied on both terrestrial and freshwater animal proteins. Even though dental calculus analysis was, in part, hindered by the amount of mineral deposit available on the teeth, tooth macrowear study suggests that the dietary habits of the individuals included plant foods. Moreover, differences in macrowear patterns of lower second molars have been documented between Neanderthals and modern humans in the present sample, due to a prevalence of Buccal wear among the former as opposed to higher values of Lingual wear in modern human teeth.

DISCUSSION: Isotopic analyses have emphasized the contribution of animal proteins in the diet of the three foragers from the Eastern Alpine region. The possible intake of carbohydrate-rich plant foods, suggested by the retrieval of plant remains in dental calculus, is supported by the signal of macrowear analysis. Moreover, the latter method indicates that the distribution of macrowear in lower second molars (M2 s) allows us to discriminate between Neanderthals and modern humans within the present reference sample. Overall, our results show these three prehistoric hunter-gatherers were well adapted to the environment in which they lived exploiting many natural resources.},
}

Animals
Carbon Isotopes/analysis
Dental Calculus/chemistry
Diet/*history
Feeding Behavior/*physiology
History, Ancient
Humans
Italy
Molar/pathology
Neanderthals
Paleontology
Tooth Wear/pathology

@article {pmid32901061,
year = {2020},
author = {Picin, A and Hajdinjak, M and Nowaczewska, W and Benazzi, S and Urbanowski, M and Marciszak, A and Fewlass, H and Socha, P and Stefaniak, K and Żarski, M and Wiśniewski, A and Hublin, JJ and Nadachowski, A and Talamo, S},
title = {New perspectives on Neanderthal dispersal and turnover from Stajnia Cave (Poland).},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {14778},
pmid = {32901061},
issn = {2045-2322},
mesh = {Animals ; Archaeology ; *Caves ; DNA, Mitochondrial/*analysis/genetics ; *Fossils ; Humans ; Neanderthals/classification/*genetics ; Phylogeny ; Poland ; Radiometric Dating ; Sequence Analysis, DNA ; Tooth/*anatomy & histology/physiology ; },
abstract = {The Micoquian is the broadest and longest enduring cultural facies of the Late Middle Palaeolithic that spread across the periglacial and boreal environments of Europe between Eastern France, Poland, and Northern Caucasus. Here, we present new data from the archaeological record of Stajnia Cave (Poland) and the paleogenetic analysis of a Neanderthal molar S5000, found in a Micoquian context. Our results demonstrate that the mtDNA genome of Stajnia S5000 dates to MIS 5a making the tooth the oldest Neanderthal specimen from Central-Eastern Europe. Furthermore, S5000 mtDNA has the fewest number of differences to mtDNA of Mezmaiskaya 1 Neanderthal from Northern Caucasus, and is more distant from almost contemporaneous Neanderthals of Scladina and Hohlenstein-Stadel. This observation and the technological affinity between Poland and the Northern Caucasus could be the result of increased mobility of Neanderthals that changed their subsistence strategy for coping with the new low biomass environments and the increased foraging radius of gregarious animals. The Prut and Dniester rivers were probably used as the main corridors of dispersal. The persistence of the Micoquian techno-complex in South-Eastern Europe infers that this axis of mobility was also used at the beginning of MIS 3 when a Neanderthal population turnover occurred in the Northern Caucasus.},
}

Animals
Archaeology
*Caves
DNA, Mitochondrial/*analysis/genetics
*Fossils
Humans
Neanderthals/classification/*genetics
Phylogeny
Poland
Radiometric Dating
Sequence Analysis, DNA
Tooth/*anatomy & histology/physiology

@article {pmid32889336,
year = {2020},
author = {Romandini, M and Oxilia, G and Bortolini, E and Peyrégne, S and Delpiano, D and Nava, A and Panetta, D and Di Domenico, G and Martini, P and Arrighi, S and Badino, F and Figus, C and Lugli, F and Marciani, G and Silvestrini, S and Menghi Sartorio, JC and Terlato, G and Hublin, JJ and Meyer, M and Bondioli, L and Higham, T and Slon, V and Peresani, M and Benazzi, S},
title = {A late Neanderthal tooth from northeastern Italy.},
journal = {Journal of human evolution},
volume = {147},
number = {},
pages = {102867},
doi = {10.1016/j.jhevol.2020.102867},
pmid = {32889336},
issn = {1095-8606},
abstract = {The site of Riparo Broion (Vicenza, northeastern Italy) preserves a stratigraphic sequence documenting the Middle-to-Upper Paleolithic transition, in particular the final Mousterian and the Uluzzian cultures. In 2018, a human tooth was retrieved from a late Mousterian level, representing the first human remain ever found from this rock shelter (Riparo Broion 1). Here, we provide the morphological description and taxonomic assessment of Riparo Broion 1 with the support of classic and virtual morphology, 2D and 3D analysis of the topography of enamel thickness, and DNA analysis. The tooth is an exfoliated right upper deciduous canine, and its general morphology and enamel thickness distribution support attribution to a Neanderthal child. Correspondingly, the mitochondrial DNA sequence from Riparo Broion 1 falls within the known genetic variation of Late Pleistocene Neanderthals, in accordance with newly obtained radiocarbon dates that point to approximately 48 ka cal BP as the most likely minimum age for this specimen. The present work describes novel and direct evidence of the late Neanderthal occupation in northern Italy that preceded the marked cultural and technological shift documented by the Uluzzian layers in the archaeological sequence at Riparo Broion. Here, we provide a new full morphological, morphometric, and taxonomic analysis of Riparo Broion 1, in addition to generating the wider reference sample of Neanderthal and modern human upper deciduous canines. This research contributes to increasing the sample of fossil remains from Italy, as well as the number of currently available upper deciduous canines, which are presently poorly documented in the scientific literature.},
}

@article {pmid32874601,
year = {2020},
author = {Amos, W},
title = {Signals interpreted as archaic introgression appear to be driven primarily by faster evolution in Africa.},
journal = {Royal Society open science},
volume = {7},
number = {7},
pages = {191900},
pmid = {32874601},
issn = {2054-5703},
abstract = {Non-African humans appear to carry a few per cent archaic DNA due to ancient inter-breeding. This modest legacy and its likely recent timing imply that most introgressed fragments will be rare and hence will occur mainly in the heterozygous state. I tested this prediction by calculating D statistics, a measure of legacy size, for pairs of humans where one of the pair was conditioned always to be either homozygous or heterozygous. Using coalescent simulations, I confirmed that conditioning the non-African to be heterozygous increased D, while conditioning the non-African to be homozygous reduced D to zero. Repeating with real data reveals the exact opposite pattern. In African-non-African comparisons, D is near-zero if the African individual is held homozygous. Conditioning one of two Africans to be either homozygous or heterozygous invariably generates large values of D, even when both individuals are drawn from the same population. Invariably, the African with more heterozygous sites (conditioned heterozygous > unconditioned > conditioned homozygous) appears less related to the archaic. By contrast, the same analysis applied to pairs of non-Africans always yields near-zero D, showing that conditioning does not create large D without an underlying signal to expose. Large D values in humans are therefore driven almost entirely by heterozygous sites in Africans acting to increase divergence from related taxa such as Neanderthals. In comparison with heterozygous Africans, individuals that lack African heterozygous sites, whether non-African or conditioned homozygous African, always appear more similar to archaic outgroups, a signal previously interpreted as evidence for introgression. I hope these analyses will encourage others to consider increased divergence as well as increased similarity to archaics as mechanisms capable of driving asymmetrical base-sharing.},
}

@article {pmid32859969,
year = {2020},
author = {Yousefi, M and Heydari-Guran, S and Kafash, A and Ghasidian, E},
title = {Species distribution models advance our knowledge of the Neanderthals' paleoecology on the Iranian Plateau.},
journal = {Scientific reports},
volume = {10},
number = {1},
pages = {14248},
pmid = {32859969},
issn = {2045-2322},
mesh = {Animals ; Archaeology ; Asia, Western ; Demography/*trends ; Ecology/history ; Europe ; Fossils ; Goats ; History, Ancient ; Humans ; Iran ; Models, Statistical ; Neanderthals/*physiology ; Paleontology/methods ; Sheep ; },
abstract = {Neanderthals (Homo neanderthalensis) were distributed across a vast region from Europe to western and Central Asia. The Neanderthals' paleoecology and distribution has been extensively studied in Europe where the species originated. However, very little is known about their paleoecology in south-western Asia. Here, we employed species distribution modelling and 45 Middle Palaeolithic (c. 200,000-40,000 years BCE) sites location associated with fossil and/or lithic artefacts made by the Neanderthals to examine the expansion of the Neanderthals on the Iranian Plateau in south-western Asia. We estimated the niche overlap between Neanderthals and wild goat, wild sheep and Persian gazelle by modelling their past distribution using 200, 143 and 110 occurrence records respectively. The results show that Neanderthals had highest niche overlap with wild goat in the study area. This analysis revealed that the most suitable Neanderthals' habitats in south-western Asia were located in the Zagros Mountains stretches from north-western and western and some isolated patches in the central parts of the Iranian Plateau. The annual precipitation and maximum temperature of the warmest month were the most important predictor of the species' distribution. This finding shows that the southern edge of the Neanderthals distribution was limited by warm summer. Our results provide important information for future field investigations and excavations in the area.},
}

Animals
Archaeology
Asia, Western
Demography/*trends
Ecology/history
Europe
Fossils
Goats
History, Ancient
Humans
Iran
Models, Statistical
Neanderthals/*physiology
Paleontology/methods
Sheep

@article {pmid32853200,
year = {2020},
author = {Mughal, MR and Koch, H and Huang, J and Chiaromonte, F and DeGiorgio, M},
title = {Learning the properties of adaptive regions with functional data analysis.},
journal = {PLoS genetics},
volume = {16},
number = {8},
pages = {e1008896},
pmid = {32853200},
issn = {1553-7404},
support = {R35 GM128590/GM/NIGMS NIH HHS/United States ; T32 GM102057/GM/NIGMS NIH HHS/United States ; F31 HG010574/HG/NHGRI NIH HHS/United States ; },
mesh = {Animals ; DNA-Binding Proteins/genetics ; European Continental Ancestry Group/*genetics ; Genetic Variation ; Humans ; Membrane Transport Proteins ; *Models, Genetic ; *Mutation Rate ; Neanderthals/genetics ; Selection, Genetic ; Software ; },
abstract = {Identifying regions of positive selection in genomic data remains a challenge in population genetics. Most current approaches rely on comparing values of summary statistics calculated in windows. We present an approach termed SURFDAWave, which translates measures of genetic diversity calculated in genomic windows to functional data. By transforming our discrete data points to be outputs of continuous functions defined over genomic space, we are able to learn the features of these functions that signify selection. This enables us to confidently identify complex modes of natural selection, including adaptive introgression. We are also able to predict important selection parameters that are responsible for shaping the inferred selection events. By applying our model to human population-genomic data, we recapitulate previously identified regions of selective sweeps, such as OCA2 in Europeans, and predict that its beneficial mutation reached a frequency of 0.02 before it swept 1,802 generations ago, a time when humans were relatively new to Europe. In addition, we identify BNC2 in Europeans as a target of adaptive introgression, and predict that it harbors a beneficial mutation that arose in an archaic human population that split from modern humans within the hypothesized modern human-Neanderthal divergence range.},
}

Animals
DNA-Binding Proteins/genetics
European Continental Ancestry Group/*genetics
Genetic Variation
Humans
Membrane Transport Proteins
*Models, Genetic
*Mutation Rate
Neanderthals/genetics
Selection, Genetic
Software

@article {pmid32839541,
year = {2020},
author = {Telis, N and Aguilar, R and Harris, K},
title = {Selection against archaic hominin genetic variation in regulatory regions.},
journal = {Nature ecology & evolution},
volume = {4},
number = {11},
pages = {1558-1566},
doi = {10.1038/s41559-020-01284-0},
pmid = {32839541},
issn = {2397-334X},
support = {R35 GM133428/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Biological Evolution ; *Hominidae/genetics ; Humans ; *Neanderthals/genetics ; Regulatory Sequences, Nucleic Acid ; Selection, Genetic ; },
abstract = {Traces of Neandertal and Denisovan DNA persist in the modern human gene pool, but have been systematically purged by natural selection from genes and other functionally important regions. This implies that many archaic alleles harmed the fitness of hybrid individuals, but the nature of this harm is poorly understood. Here, we show that enhancers contain less Neandertal and Denisovan variation than expected given the background selection they experience, suggesting that selection acted to purge these regions of archaic alleles that disrupted their gene regulatory functions. We infer that selection acted mainly on young archaic variation that arose in Neandertals or Denisovans shortly before their contact with humans; enhancers are not depleted of older variants found in both archaic species. Some types of enhancer appear to have tolerated introgression better than others; compared with tissue-specific enhancers, pleiotropic enhancers show stronger depletion of archaic single-nucleotide polymorphisms. To some extent, evolutionary constraint is predictive of introgression depletion, but certain tissues' enhancers are more depleted of Neandertal and Denisovan alleles than expected given their comparative tolerance to new mutations. Foetal brain and muscle are the tissues whose enhancers show the strongest depletion of archaic alleles, but only brain enhancers show evidence of unusually stringent purifying selection. We conclude that epistatic incompatibilities between human and archaic alleles are needed to explain the degree of archaic variant depletion from foetal muscle enhancers, perhaps due to divergent selection for higher muscle mass in archaic hominins compared with humans.},
}

Animals
Biological Evolution
*Hominidae/genetics
Humans
*Neanderthals/genetics
Regulatory Sequences, Nucleic Acid
Selection, Genetic

@article {pmid32817536,
year = {2020},
author = {Bard, E and Heaton, TJ and Talamo, S and Kromer, B and Reimer, RW and Reimer, PJ},
title = {Extended dilation of the radiocarbon time scale between 40,000 and 48,000 y BP and the overlap between Neanderthals and Homo sapiens.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {117},
number = {35},
pages = {21005-21007},
pmid = {32817536},
issn = {1091-6490},
mesh = {Animals ; Calibration/standards ; Fossils ; Humans ; Neanderthals ; Paleontology/*methods ; Radiometric Dating/*methods ; },
abstract = {The new radiocarbon calibration curve (IntCal20) allows us to calculate the gradient of the relationship between 14C age and calendar age over the past 55 millennia before the present (55 ka BP). The new gradient curve exhibits a prolonged and prominent maximum between 48 and 40 ka BP during which the radiocarbon clock runs almost twice as fast as it should. This radiocarbon time dilation is due to the increase in the atmospheric 14C/12C ratio caused by the 14C production rise linked to the transition into the Laschamp geomagnetic excursion centered around 41 ka BP. The major maximum in the gradient from 48 to 40 ka BP is a new feature of the IntCal20 calibration curve, with far-reaching impacts for scientific communities, such as prehistory and paleoclimatology, relying on accurate ages in this time range. To illustrate, we consider the duration of the overlap between Neanderthals and Homo sapiens in Eurasia.},
}

Animals
Calibration/standards
Fossils
Humans
Neanderthals
Paleontology/*methods
Radiometric Dating/*methods

@article {pmid32813722,
year = {2020},
author = {Delpiano, D and Uthmeier, T},
title = {Techno-functional and 3D shape analysis applied for investigating the variability of backed tools in the Late Middle Paleolithic of Central Europe.},
journal = {PloS one},
volume = {15},
number = {8},
pages = {e0236548},
pmid = {32813722},
issn = {1932-6203},
mesh = {Animals ; Archaeology/*instrumentation ; Artifacts ; Behavior Rating Scale ; Fossils/*diagnostic imaging ; Humans ; Neanderthals ; Paleontology/*instrumentation ; Technology/*instrumentation ; Tool Use Behavior/classification ; },
abstract = {In the Late Middle Paleolithic of Central Europe, two main cultural complexes have been distinguished: the Micoquian or Keilmessergruppe (KMG), and the Mousterian. Their differences mainly consist in the frequence of some retouched tools and the presence of bifacial technology. When these industries coexist, one element of discussion is the application of different concepts to manufacture tools with the same techno-functionality. This is particularly true for backed artifacts, such as Keilmesser (backed, asymmetrical bifacially-shaped knives) opposed to flake-tools equipped with a natural or knapped back. We conducted a techno-functional analysis of the backed tools from the G-Layer-Complex of Sesselfelsgrotte, one of the main Late Middle Paleolithic sequences in Central Europe, characterized by a combination of KMG and Mousterian aspects. In order to better understand the morpho-metrical data, 3D scans were used for recording technical features and performing semi-automatic geometric morphometrics. Results indicate that the techno-functional schemes of Keilmesser show a moderate variability and often overlap with the schemes of other typological groups. Within bifacial backed knives, a process of imitation of unifacial flake tools' functionaly was recognized particularly in the cutting edge manufacturing. Keilmesser proved to be the long-life, versatile version of backed flake-tools, also due to the recurrent valence as both tool and core. This is why Keilmesser represent an ideal strategic blank when a mobile and multi-functional tool is needed. Based on these data, it is assumed that the relationship between Mousterian and KMG is deeply rooted and the emergence of KMG aspects could be related to constrained situations characterizing the long cold stages of the Early Weichselian. A higher regional mobility caused by the comparably low predictability of resources characterized the subsistence tactics of Neanderthal groups especially at the borders of their overall distribution. For this reason, Keilmesser could have represented an ecological answer before possibly becoming a marker of cultural identity.},
}

Animals
Archaeology/*instrumentation
Artifacts
Behavior Rating Scale
Fossils/*diagnostic imaging
Humans
Neanderthals
Paleontology/*instrumentation
Technology/*instrumentation
Tool Use Behavior/classification

@article {pmid32805525,
year = {2020},
author = {Torres-Tamayo, N and Schlager, S and García-Martínez, D and Sanchis-Gimeno, JA and Nalla, S and Ogihara, N and Oishi, M and Martelli, S and Bastir, M},
title = {Three-dimensional geometric morphometrics of thorax-pelvis covariation and its potential for predicting the thorax morphology: A case study on Kebara 2 Neandertal.},
journal = {Journal of human evolution},
volume = {147},
number = {},
pages = {102854},
doi = {10.1016/j.jhevol.2020.102854},
pmid = {32805525},
issn = {1095-8606},
abstract = {The skeletal torso is a complex structure of outstanding importance in understanding human body shape evolution, but reconstruction usually entails an element of subjectivity as researchers apply their own anatomical expertise to the process. Among different fossil reconstruction methods, 3D geometric morphometric techniques have been increasingly used in the last decades. Two-block partial least squares analysis has shown great potential for predicting missing elements by exploiting the covariation between two structures (blocks) in a reference sample: one block can be predicted from the other one based on the strength of covariation between blocks. The first aim of this study is to test whether this predictive approach can be used for predicting thorax morphologies from pelvis morphologies within adult Homo sapiens reference samples with known covariation between the thorax and the pelvis. The second aim is to apply this method to Kebara 2 Neandertal (Israel, ∼60 ka) to predict its thorax morphology using two different pelvis reconstructions as predictors. We measured 134 true landmarks, 720 curve semilandmarks, and 160 surface semilandmarks on 60 3D virtual torso models segmented from CT scans. We conducted three two-block partial least squares analyses between the thorax (block 1) and the pelvis (block 2) based on the H. sapiens reference samples after performing generalized Procrustes superimposition on each block separately. Comparisons of these predictions in full shape space by means of Procrustes distances show that the male-only predictive model yields the most reliable predictions within modern humans. In addition, Kebara 2 thorax predictions based on this model concur with the thorax morphology proposed for Neandertals. The method presented here does not aim to replace other techniques, but to rather complement them through quantitative prediction of a virtual 'scaffold' to articulate the thoracic fossil elements, thus extending the potential of missing data estimation beyond the methods proposed in previous works.},
}

@article {pmid32760067,
year = {2020},
author = {Hubisz, MJ and Williams, AL and Siepel, A},
title = {Mapping gene flow between ancient hominins through demography-aware inference of the ancestral recombination graph.},
journal = {PLoS genetics},
volume = {16},
number = {8},
pages = {e1008895},
pmid = {32760067},
issn = {1553-7404},
support = {R35 GM127070/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Evolution, Molecular ; *Gene Flow ; Human Migration ; Humans ; *Models, Genetic ; Neanderthals/*genetics ; Population/*genetics ; *Recombination, Genetic ; },
abstract = {The sequencing of Neanderthal and Denisovan genomes has yielded many new insights about interbreeding events between extinct hominins and the ancestors of modern humans. While much attention has been paid to the relatively recent gene flow from Neanderthals and Denisovans into modern humans, other instances of introgression leave more subtle genomic evidence and have received less attention. Here, we present a major extension of the ARGweaver algorithm, called ARGweaver-D, which can infer local genetic relationships under a user-defined demographic model that includes population splits and migration events. This Bayesian algorithm probabilistically samples ancestral recombination graphs (ARGs) that specify not only tree topologies and branch lengths along the genome, but also indicate migrant lineages. The sampled ARGs can therefore be parsed to produce probabilities of introgression along the genome. We show that this method is well powered to detect the archaic migration into modern humans, even with only a few samples. We then show that the method can also detect introgressed regions stemming from older migration events, or from unsampled populations. We apply it to human, Neanderthal, and Denisovan genomes, looking for signatures of older proposed migration events, including ancient humans into Neanderthal, and unknown archaic hominins into Denisovans. We identify 3% of the Neanderthal genome that is putatively introgressed from ancient humans, and estimate that the gene flow occurred between 200-300kya. We find no convincing evidence that negative selection acted against these regions. Finally, we predict that 1% of the Denisovan genome was introgressed from an unsequenced, but highly diverged, archaic hominin ancestor. About 15% of these "super-archaic" regions-comprising at least about 4Mb-were, in turn, introgressed into modern humans and continue to exist in the genomes of people alive today.},
}

Animals
Evolution, Molecular
*Gene Flow
Human Migration
Humans
*Models, Genetic
Neanderthals/*genetics
Population/*genetics
*Recombination, Genetic

@article {pmid32750315,
year = {2020},
author = {Course, MM and Gudsnuk, K and Smukowski, SN and Winston, K and Desai, N and Ross, JP and Sulovari, A and Bourassa, CV and Spiegelman, D and Couthouis, J and Yu, CE and Tsuang, DW and Jayadev, S and Kay, MA and Gitler, AD and Dupre, N and Eichler, EE and Dion, PA and Rouleau, GA and Valdmanis, PN},
title = {Evolution of a Human-Specific Tandem Repeat Associated with ALS.},
journal = {American journal of human genetics},
volume = {107},
number = {3},
pages = {445-460},
pmid = {32750315},
issn = {1537-6605},
support = {T32 GM007454/GM/NIGMS NIH HHS/United States ; U24 AG041689/AG/NIA NIH HHS/United States ; R01 DK078424/DK/NIDDK NIH HHS/United States ; P30 AG066509/AG/NIA NIH HHS/United States ; P50 AG005136/AG/NIA NIH HHS/United States ; R01 HG010169/HG/NHGRI NIH HHS/United States ; },
mesh = {Adaptor Proteins, Signal Transducing/*genetics ; Aged ; Alzheimer Disease/genetics/pathology ; Amyotrophic Lateral Sclerosis/*genetics/pathology ; DNA Repeat Expansion/genetics ; *Evolution, Molecular ; Female ; Gene Expression Regulation/genetics ; Humans ; Male ; Minisatellite Repeats/genetics ; Phenotype ; Species Specificity ; Tandem Repeat Sequences/*genetics ; },
abstract = {Tandem repeats are proposed to contribute to human-specific traits, and more than 40 tandem repeat expansions are known to cause neurological disease. Here, we characterize a human-specific 69 bp variable number tandem repeat (VNTR) in the last intron of WDR7, which exhibits striking variability in both copy number and nucleotide composition, as revealed by long-read sequencing. In addition, greater repeat copy number is significantly enriched in three independent cohorts of individuals with sporadic amyotrophic lateral sclerosis (ALS). Each unit of the repeat forms a stem-loop structure with the potential to produce microRNAs, and the repeat RNA can aggregate when expressed in cells. We leveraged its remarkable sequence variability to align the repeat in 288 samples and uncover its mechanism of expansion. We found that the repeat expands in the 3'-5' direction, in groups of repeat units divisible by two. The expansion patterns we observed were consistent with duplication events, and a replication error called template switching. We also observed that the VNTR is expanded in both Denisovan and Neanderthal genomes but is fixed at one copy or fewer in non-human primates. Evaluating the repeat in 1000 Genomes Project samples reveals that some repeat segments are solely present or absent in certain geographic populations. The large size of the repeat unit in this VNTR, along with our multiplexed sequencing strategy, provides an unprecedented opportunity to study mechanisms of repeat expansion, and a framework for evaluating the roles of VNTRs in human evolution and disease.},
}

Adaptor Proteins, Signal Transducing/*genetics
Aged
Alzheimer Disease/genetics/pathology
Amyotrophic Lateral Sclerosis/*genetics/pathology
DNA Repeat Expansion/genetics
*Evolution, Molecular
Female
Gene Expression Regulation/genetics
Humans
Male
Minisatellite Repeats/genetics
Phenotype
Species Specificity
Tandem Repeat Sequences/*genetics

@article {pmid32745133,
year = {2020},
author = {Örd, T and Puurand, T and Örd, D and Annilo, T and Möls, M and Remm, M and Örd, T},
title = {A human-specific VNTR in the TRIB3 promoter causes gene expression variation between individuals.},
journal = {PLoS genetics},
volume = {16},
number = {8},
pages = {e1008981},
pmid = {32745133},
issn = {1553-7404},
support = {HHSN268201000029C/HL/NHLBI NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; },
mesh = {Cell Cycle Proteins/*genetics ; Estonia/epidemiology ; Female ; Gene Expression Regulation/genetics ; *Genetic Heterogeneity ; *Genetics, Population ; Genotype ; Humans ; Male ; Minisatellite Repeats/*genetics ; Promoter Regions, Genetic ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/genetics ; RNA-Seq ; Repressor Proteins/*genetics ; Whole Genome Sequencing ; },
abstract = {Tribbles homolog 3 (TRIB3) is pseudokinase involved in intracellular regulatory processes and has been implicated in several diseases. In this article, we report that human TRIB3 promoter contains a 33-bp variable number tandem repeat (VNTR) and characterize the heterogeneity and function of this genetic element. Analysis of human populations around the world uncovered the existence of alleles ranging from 1 to 5 copies of the repeat, with 2-, 3- and 5-copy alleles being the most common but displaying considerable geographical differences in frequency. The repeated sequence overlaps a C/EBP-ATF transcriptional regulatory element and is highly conserved, but not repeated, in various mammalian species, including great apes. The repeat is however evident in Neanderthal and Denisovan genomes. Reporter plasmid experiments in human cell culture reveal that an increased copy number of the TRIB3 promoter 33-bp repeat results in increased transcriptional activity. In line with this, analysis of whole genome sequencing and RNA-Seq data from human cohorts demonstrates that the copy number of TRIB3 promoter 33-bp repeats is positively correlated with TRIB3 mRNA expression level in many tissues throughout the body. Moreover, the copy number of the TRIB3 33-bp repeat appears to be linked to known TRIB3 eQTL SNPs as well as TRIB3 SNPs reported in genetic association studies. Taken together, the results indicate that the promoter 33-bp VNTR constitutes a causal variant for TRIB3 expression variation between individuals and could underlie the results of SNP-based genetic studies.},
}

Cell Cycle Proteins/*genetics
Estonia/epidemiology
Female
Gene Expression Regulation/genetics
*Genetic Heterogeneity
*Genetics, Population
Genotype
Humans
Male
Minisatellite Repeats/*genetics
Promoter Regions, Genetic
Protein-Serine-Threonine Kinases/*antagonists & inhibitors/genetics
RNA-Seq
Repressor Proteins/*genetics
Whole Genome Sequencing

@article {pmid32735718,
year = {2020},
author = {Ríos, L and Cardoso, HFV},
title = {Comment on 'Krapina atlases suggest a high prevalence of anatomical variations in the first cervical vertebra of Neanderthals'.},
journal = {Journal of anatomy},
volume = {237},
number = {6},
pages = {1185-1188},
doi = {10.1111/joa.13268},
pmid = {32735718},
issn = {1469-7580},
abstract = {A review of the observation of an anterior cleft on the atlas of a Neanderthal from Krapina.},
}