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Genomic evidence supports an important role for selection in shaping patterns of introgression along the genome, but frameworks for understanding the evolutionary dynamics within hybrid populations that underlie these patterns have been lacking. Due to the clock-like effect of recombination in hybrids breaking up parental haplotypes, drift and selection produce predictable patterns of ancestry variation at varying spatial genomic scales through time. Here, we develop methods based on the Discrete Wavelet Transform to study the genomic scale of local ancestry variation and its association with recombination rates and show that these methods capture temporal dynamics of drift and genome-wide selection after hybridization. We apply these methods to published datasets from hybrid populations of swordtail fish (Xiphophorus) and baboons (Papio) and to inferred Neanderthal introgression in modern humans. Across systems, upward of 20% of variation in local ancestry at the broadest genomic scales can be attributed to systematic selection against introgressed alleles, consistent with strong selection acting on early-generation hybrids. Signatures of selection at fine genomic scales suggest selection over longer time scales; however, we suggest that our ability to confidently infer selection at fine scales is likely limited by inherent biases in current methods for estimating local ancestry from contiguous segments of genomic similarity. Wavelet approaches will become widely applicable as genomic data from systems with introgression become increasingly available and can help shed light on generalities of the genomic consequences of interspecific hybridization.

The emergence of the Middle Palaeolithic, and its variability over time and space are key questions in the field of prehistoric archaeology. Many sites have been documented in the south-eastern margins of the Massif central and the middle Rhône valley, a migration path that connects Northern Europe with the Mediterranean. Well-dated, long stratigraphic sequences are essential to understand Neanderthals dynamics and demise, and potential interactions with Homo sapiens in the area, such as the one displayed at the Maras rock shelter ("Abri du Maras"). The site is characterised by exceptional preservation of archaeological remains, including bones dated using radiocarbon (14C) and teeth using electron spin resonance combined with uranium series (ESR/U-series). Optically stimulated luminescence was used to date the sedimentary deposits. By combining the new ages with previous ones using Bayesian modelling, we are able to clarify the occupation time over a period spanning 200,000 years. Between ca. 250 and 40 ka, the site has been used as a long-term residence by Neanderthals, specifically during three interglacial periods: first during marine isotopic stage (MIS) 7, between 247 ± 34 and 223 ± 33 ka, and then recurrently during MIS 5 (between 127 ± 17 and 90 ± 9 ka) and MIS 3 (up to 39,280 cal BP). [ABSTRACT FROM AUTHOR]

Objectives: Grotta‐Riparo di Uluzzo C (Apulia, southern Italy) is a pivotal site for investigating the evolution of the Middle Paleolithic and the earliest phases of the Upper Paleolithic in southern Italy, as the extensive stratigraphic record of this site includes a thick Mousterian sequence followed by the Uluzzian. Here, we investigate the taxonomic affinity of seven unpublished deciduous human teeth retrieved from the site of Uluzzo C in 1960. Materials and Methods: The teeth are represented by seven plaster dental casts, which are housed at the Museo Civico di Paleontologia e Paletnologia in Maglie (Lecce, Apulia). The location of the original specimens remains unknown, rendering these casts the only human remains evidence yielded by Uluzzo C to date. Based on occlusal‐view photographs and digital models of the casts, we examined the external morphology and morphometry of the teeth, comparing them to Homo sapiens and H. neanderthalensis samples. Through geometric morphometric methods and statistical analyses, we analyzed the crown outline of the deciduous molars. Results: The teeth show morphological and morphometric features that are variably found in H. neanderthalensis, H. sapiens, or both. Specifically, crown outline analysis shows that all molars fall within H. neanderthalensis variability, except for Uluzzo 853 (lower right deciduous first molar), which falls within H. sapiens variability. Discussion: This study provides the first taxonomic assessment of the hominin teeth from Uluzzo C. The results contribute additional insights into the Paleolithic peopling of southern Italy during a crucial period marked by the persistence of post‐Tyrrhenian Neanderthal techno‐complexes and the arrival of H. sapiens. [ABSTRACT FROM AUTHOR]

Because it is often assumed that fundamental behavioral differences distinguish Neanderthals and Homo sapiens, the ability to structure space within the sites they occupied into distinct activity areas is often invoked as a key distinctive trait of our species. However, this behavior has never been assessed for both groups at a single site, hindering direct comparisons to date. To help resolve this question, this study uses a single methodology to evaluate the spatial organization in the Protoaurignacian levels (A1-A2, associated with Homo sapiens) and the latest Mousterian levels (MS1-MS2, associated with Neanderthals) at Riparo Bombrini (Liguria, Italy) to assess the changes over these three stratigraphic units vis a vis other information about site use. Combining GIS and quantitative methods allows the study of the spatial distribution of plotted finds and features in these levels, showing that Neandertals and Homo sapiens organized their living spaces in accordance with the duration of occupation, the occupation intensity, the tool assemblage and the faunal exploitation. Our results indicate that there is a logic behind the distribution of plotted finds and the use of the space, suggesting comparable cognitive capacities for both anatomically modern humans and Neanderthals. This contributes further data that undermines the notion of 'behavioral modernity' as a useful heuristic in human origins research. [ABSTRACT FROM AUTHOR]

Abstract The emergence of the Middle Palaeolithic, and its variability over time and space are key questions in the field of prehistoric archaeology. Many sites have been documented in the south-eastern margins of the Massif central and the middle Rhône valley, a migration path that connects Northern Europe with the Mediterranean. Well-dated, long stratigraphic sequences are essential to understand Neanderthals dynamics and demise, and potential interactions with Homo sapiens in the area, such as the one displayed at the Maras rock shelter (“Abri du Maras”). The site is characterised by exceptional preservation of archaeological remains, including bones dated using radiocarbon (14C) and teeth using electron spin resonance combined with uranium series (ESR/U-series). Optically stimulated luminescence was used to date the sedimentary deposits. By combining the new ages with previous ones using Bayesian modelling, we are able to clarify the occupation time over a period spanning 200,000 years. Between ca. 250 and 40 ka, the site has been used as a long-term residence by Neanderthals, specifically during three interglacial periods: first during marine isotopic stage (MIS) 7, between 247 ± 34 and 223 ± 33 ka, and then recurrently during MIS 5 (between 127 ± 17 and 90 ± 9 ka) and MIS 3 (up to 39,280 cal BP).

Immunoglobulins (Igs) have a crucial role in humoral immunity. Two recent studies have reported a high-frequency Neanderthal-introgressed haplotype throughout Eurasia and a high-frequency Neanderthal-introgressed haplotype specific to southern East Asia at the immunoglobulin heavy-chain (IGH) gene locus on chromosome 14q32.33. Surprisingly, we found the previously reported high-frequency Neanderthal-introgressed haplotype does not exist throughout Eurasia. Instead, our study identified two distinct high-frequency haplotypes of putative Neanderthal origin in East Asia and Europe, although they shared introgressed alleles. Notably, the alleles of putative Neanderthal origin reduced the expression of IGHG1 and increased the expression of IGHG2 and IGHG3 in various tissues. These putatively introgressed alleles also affected the production of IgG1 upon antigen stimulation and increased the risk of systemic lupus erythematosus. Additionally, the greatest genetic differentiation across the whole genome between southern and northern East Asians was observed for the East Asian haplotype of putative Neanderthal origin. The frequency decreased from southern to northern East Asia and correlated positively with the genome-wide proportion of southern East Asian ancestry, indicating that this putative positive selection likely occurred in the common ancestor of southern East Asian populations before the admixture with northern East Asian populations. [ABSTRACT FROM AUTHOR]

Ascorbic acid functions as an antioxidant and facilitates other biochemical processes such as collagen triple helix formation, and iron uptake by cells. Animals which endogenously produce ascorbic acid have a functional gulonolactone oxidase gene (GULO); however, humans have a GULO pseudogene (GULOP) and depend on dietary ascorbic acid. In this study, the conservation of GULOP sequences in the primate haplorhini suborder were investigated and compared to the GULO sequences belonging to the primates strepsirrhini suborder. Phylogenetic analysis suggested that the conserved GULOP exons in the haplorhini primates experienced a high rate of mutations following the haplorhini/strepsirrhini divergence. This high mutation rate has decreased during the evolution of the haplorhini primates. Additionally, indels of the haplorhini GULOP sequences were conserved across the suborder. A separate analysis for GULO sequences and well-conserved GULOP sequences focusing on placental mammals identified an in-frame GULO sequence in the Brazilian guinea pig, and a potential GULOP sequence in the pika. Similar to haplorhini primates, the guinea pig and lagomorph species have experienced a high substitution rate when compared to the mammals used in this study. A shared synteny to examine the conservation of local genes near GULO/GULOP identified a conserved inversion around the GULO/GULOP locus between the haplorhini and strepsirrhini primates. Fischer's exact test did not support an association between GULOP and the chromosomal inversion. Mauve alignment showed that the inversion of the length of the syntenic block that the GULO/GULOP genes belonged to was variable. However, there were frequent rearrangements around ~ 2 million base pairs adjacent to GULOP involving the KIF13B and MSRA genes. These data may suggest that genes acquiring deleterious mutations in the coding sequence may respond to these deleterious mutations with rapid substitution rates. [ABSTRACT FROM AUTHOR]

Abstract Background The human lineage has undergone a postcranial skeleton gracilization (i.e. lower bone mass and strength relative to body size) compared to other primates and archaic populations such as the Neanderthals. This gracilization has been traditionally explained by differences in the mechanical load that our ancestors exercised. However, there is growing evidence that gracilization could also be genetically influenced. Results We have analyzed the LRP5 gene, which is known to be associated with high bone mineral density conditions, from an evolutionary and functional point of view. Taking advantage of the published genomes of archaic Homo populations, our results suggest that this gene has a complex evolutionary history both between archaic and living humans and within living human populations. In particular, we identified the presence of different selective pressures in archaics and extant modern humans, as well as evidence of positive selection in the African and South East Asian populations from the 1000 Genomes Project. Furthermore, we observed a very limited evidence of archaic introgression in this gene (only at three haplotypes of East Asian ancestry out of the 1000 Genomes), compatible with a general erasing of the fingerprint of archaic introgression due to functional differences in archaics compared to extant modern humans. In agreement with this hypothesis, we observed private mutations in the archaic genomes that we experimentally validated as putatively increasing bone mineral density. In particular, four of five archaic missense mutations affecting the first β-propeller of LRP5 displayed enhanced Wnt pathway activation, of which two also displayed reduced negative regulation. Conclusions In summary, these data suggest a genetic component contributing to the understanding of skeletal differences between extant modern humans and archaic Homo populations.

Background: The human lineage has undergone a postcranial skeleton gracilization (i.e. lower bone mass and strength relative to body size) compared to other primates and archaic populations such as the Neanderthals. This gracilization has been traditionally explained by differences in the mechanical load that our ancestors exercised. However, there is growing evidence that gracilization could also be genetically influenced. Results: We have analyzed the LRP5 gene, which is known to be associated with high bone mineral density conditions, from an evolutionary and functional point of view. Taking advantage of the published genomes of archaic Homo populations, our results suggest that this gene has a complex evolutionary history both between archaic and living humans and within living human populations. In particular, we identified the presence of different selective pressures in archaics and extant modern humans, as well as evidence of positive selection in the African and South East Asian populations from the 1000 Genomes Project. Furthermore, we observed a very limited evidence of archaic introgression in this gene (only at three haplotypes of East Asian ancestry out of the 1000 Genomes), compatible with a general erasing of the fingerprint of archaic introgression due to functional differences in archaics compared to extant modern humans. In agreement with this hypothesis, we observed private mutations in the archaic genomes that we experimentally validated as putatively increasing bone mineral density. In particular, four of five archaic missense mutations affecting the first β-propeller of LRP5 displayed enhanced Wnt pathway activation, of which two also displayed reduced negative regulation. Conclusions: In summary, these data suggest a genetic component contributing to the understanding of skeletal differences between extant modern humans and archaic Homo populations. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer is one of the most common cancer types in males and rs12621278:A > G has been suggested to be associated with this disease by previous genome‐wide association studies. One thousand genomes project data analysis indicated that rs12621278:A > G is within two long‐core haplotypes. However, the origin, causal variant(s), and molecular function of these haplotypes were remaining unclear. Materials and Methods: Population genetics analysis and functional genomics work was performed for this locus. Results: Phylogeny analysis verified that the rare haplotype is derived from Neanderthal introgression. Genome annotation suggested that three genetic variants in the core haplotypes, rs116108611:G > A, rs139972066:AAAAAAAA > AAAAAAAAA, and rs3835124:ATTTATT > ATT, are located in functional regions. Luciferase assay indicated that rs139972066:AAAAAAAA > AAAAAAAAA and rs116108611:G > A are not able to alter ITGA6 (integrin alpha 6) and ITGA6 antisense RNA 1 expression, respectively. In contrast, rs3835124:ATTTATT > ATT can significantly influence PDK1 (pyruvate dehydrogenase kinase 1) expression, which was verified by expression quantitative trait locus analysis. This genetic variant can alter transcription factor cut like homeobox 1 interaction efficiency. The introgressed haplotype was observed to be subject to positive selection in East Asian populations. The molecular function of the haplotype suggested that Neanderthal should be with lower PDK1 expression and further different energy homeostasis from modern human. Conclusion: This study provided new insight into the contribution of Neanderthal introgression to human phenotypes. [ABSTRACT FROM AUTHOR]

Ancient DNA provides a powerful window into the biology of extant and extinct species, including humans' closest relatives: Denisovans and Neanderthals. Here, we review what is known about archaic hominin phenotypes from genomic data and how those inferences have been made. We contend that understanding the influence of variants on lower-level molecular phenotypes-such as gene expression and protein function-is a promising approach to using ancient DNA to learn about archaic hominin traits. Molecular phenotypes have simpler genetic architectures than organism-level complex phenotypes, and this approach enables moving beyond association studies by proposing hypotheses about the effects of archaic variants that are testable in model systems. The major challenge to understanding archaic hominin phenotypes is broadening our ability to accurately map genotypes to phenotypes, but ongoing advances ensure that there will be much more to learn about archaic hominin phenotypes from their genomes.

Background: We tackle the problem of estimating species TMRCAs (Time to Most Recent Common Ancestor), given a genome sequence from each species and a large known phylogenetic tree with a known structure (typically from one of the species). The number of transitions at each site from the first sequence to the other is assumed to be Poisson distributed, and only the parity of the number of transitions is observed. The detailed phylogenetic tree contains information about the transition rates in each site. We use this formulation to develop and analyze multiple estimators of the species' TMRCA. To test our methods, we use mtDNA substitution statistics from the well-established Phylotree as a baseline for data simulation such that the substitution rate per site mimics the real-world observed rates. Results: We evaluate our methods using simulated data and compare them to the Bayesian optimizing software BEAST2, showing that our proposed estimators are accurate for a wide range of TMRCAs and significantly outperform BEAST2. We then apply the proposed estimators on Neanderthal, Denisovan, and Chimpanzee mtDNA genomes to better estimate their TMRCA with modern humans and find that their TMRCA is substantially later, compared to values cited recently in the literature. Conclusions: Our methods utilize the transition statistics from the entire known human mtDNA phylogenetic tree (Phylotree), eliminating the requirement to reconstruct a tree encompassing the specific sequences of interest. Moreover, they demonstrate notable improvement in both running speed and accuracy compared to BEAST2, particularly for earlier TMRCAs like the human-Chimpanzee split. Our results date the human – Neanderthal TMRCA to be ∼ 408 , 000 years ago, considerably later than values cited in other recent studies. [ABSTRACT FROM AUTHOR]

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Bone retouchers are a technological appliance used to perfect lithic tools efficiently. They are most frequently found in Middle Palaeolithic contexts. In this paper, we present a group of bone retouchers from the Mousterian Level XV of the Sopeña rock shelter (Asturias, Spain). The bone part preferred was the middle part of the shaft of long bones: Most of them are on metacarpals, followed by metatarsals, femurs, and tibias. The most used animal species is adult red deer. These retouchers have either one, two, or three active areas, with a central disposition. The impact marks are close together; oval pits are common, as well as straight, sinuous, and irregular grooves. The surfaces on these marks appear pitted and scaled. There are indications that the bones employed were relatively fresh. The length, width, and thickness of those bone fragments seem to be the determining factor when choosing them to be used as retouchers in the process of finishing lithic tools. The formats documented in Sopeña Level XV are similar to those found in other Mousterian sites in Iberia, although there is a certain variability regarding their width. The Neanderthals of Sopeña acquired the raw material for these retouchers from the faunal remains generated in the process of butchering and eating the animals. These retouchers were used as implements to perfect lithic tools made mainly on quartzite, and they were used repeatedly and maybe for a long time. [ABSTRACT FROM AUTHOR]

Understanding the relationship between Neanderthal groups and their environment and they it is essential to comprehending their ways of life. In this article, we use both zooarchaeology and taphonomy to study the fauna assemblages found in Level 4 of Prado Vargas Cave (Cornejo, Burgos, Spain). The results point to a site in which the main accumulating agent was Neanderthal groups, who transported small- and medium-sized animal carcasses—with deer as the dominant taxon—according to their general utility to systematically and intensely exploit the major muscle bundles, bone marrow, skin, and tendons. According to dental microwear analysis, reiterated and prolonged occupations occurred in diverse moments, suggesting that the site was used most often as a long-term campsite. We detected a minimal amount of carnivore activity, who accessed the cave during periods of human absence and modified some of the remains left by the Neanderthals. Together, this information indicates that Prado Vargas is a key site to understand the dynamics of the Neanderthals in the linking area between the Castillan Plateau and the Cantabrian Range. [ABSTRACT FROM AUTHOR]

The complexity of the human brain creates a spectrum of sophisticated behavioral repertoires, such as language, tool use, self-awareness, symbolic thought, cultural learning, and consciousness. Understanding how the human brain achieves that has been a longstanding challenge for neuroscientists and may bring insights into the evolution of human cognition and disease states. Human pluripotent stem cells could differentiate into specialized cell types and tissues in vitro. From this pluripotent state, it is possible to generate models of the human brain, such as brain organoids. The recent observation that brain organoids can spontaneously develop complex neural network activity in a dish can help one understand how neural network oscillations evolve and vary between normal and disease states. Moreover, this finding can be leveraged to other applications outside medicine, including engineering and artificial intelligence. However, as the brain model technology becomes more complex, it raises a series of ethical and moral dilemmas. This article discusses the status of this technology, some of its current limitations, and a vision of the future. [ABSTRACT FROM AUTHOR]

The Tibetan Plateau is populated by diverse ethnic groups, but most of them are underrepresented in genomics studies compared with the Tibetans (TIB). Here, to gain further insight into the genetic diversity and evolutionary history of the people living in the Tibetan Plateau, we sequenced 54 whole genomes of the Deng people with high coverage (30–60×) and analyzed the data together with that of TIB and Sherpas, as well as 968 ancient Asian genomes and available archaic and modern human data. We identified 17.74 million novel single-nucleotide variants from the newly sequenced genomes, although the Deng people showed reduced genomic diversity and a relatively small effective population size. Compared with the other Tibetan highlander groups which are highly admixed, the Deng people are dominated by a sole ancestry that could be traced to some ancient northern East Asian populations. The divergence between Deng and Tibetan people (∼4,700–7,200 years) was more recent than that between highlanders and the Han Chinese (Deng-HAN, ∼9,000–14,000 years; TIB-HAN, 7,200–10,000 years). Adaptive genetic variants (AGVs) identified in the Deng are only partially shared with those previously reported in the TIB like HLA-DQB1 , whereas others like KLHL12 were not reported in TIB. In contrast, the top candidate genes harboring AGVs as previously identified in TIB, like EPAS1 and EGLN1 , do not show strong positive selection signals in Deng. Interestingly, Deng also showed a different archaic introgression scenario from that observed in the TIB. Our results suggest that convergent adaptation might be prevalent on the Tibetan Plateau. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Xinyang Normal University Natural Science Edition is the property of Journal of Xinyang Normal University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To discuss a Neandertal pathological adult first pollical proximal phalanx (I2-104) from the Baume de Moula-Guercy (Ardèche, France) and evaluate the possible causes of this pathology. Macroscopic analyses of external features, as well as CT imaging, were used in the analysis The presence of asymmetric eburnation on the distal epiphysis associated with an osteophyte on the palmar surface, as well as the absence of periosteal bone reaction visible on CT images, is consistent with osteoarthritis. Osteoarthritis (OA) can have different origins and the cause is difficult to identify. The pathology of the Moula-Guercy I2-104 phalanx may be due to a genetic predisposition for OA known in Neandertals and associated with short limb bones. The OA could have been aggravated by the age of this individual and by an inflammatory reaction caused by repeated movements and intense vibrations provoked by high-frequency knapping or by other use of the hands The I2-104 phalanx is the first Neandertal pollical phalanx known to display OA, although joints of this bone are frequently affected by this pathology in modern humans. Thus, greater insight into the presence and consequences of Neandertal behaviors is offered It is impossible to give a definitive conclusion on the cause(s) of the OA in this case. More data is needed concerning OA within Neandertals and its relationship with behavior and genetics. [ABSTRACT FROM AUTHOR]

The Neanderthal and Denisovan genomes enabled the discovery of sequences that differ between modern and archaic humans, the majority of which are noncoding. However, our understanding of the regulatory consequences of these differences remains limited, in part due to the decay of regulatory marks in ancient samples. Here, we used a massively parallel reporter assay in embryonic stem cells, neural progenitor cells, and bone osteoblasts to investigate the regulatory effects of the 14,042 single-nucleotide modern human-specific variants. Overall, 1791 (13%) of sequences containing these variants showed active regulatory activity, and 407 (23%) of these drove differential expression between human groups. Differentially active sequences were associated with divergent transcription factor binding motifs, and with genes enriched for vocal tract and brain anatomy and function. This work provides insight into the regulatory function of variants that emerged along the modern human lineage and the recent evolution of human gene expression.

The Denisova man is an extinct human-like member of the genus Homo. In March 2010 it was announced that the remains of a young individual who lived approx. 50,000 years ago had been found in the Denisova Cave in the Altai Mountains – an area that was inhabited by Neanderthals and modern humans around the same time. The presence of Denisova man has been also found as far south as Laos. Denisova man is a descendant of hominids migrants from Africa. So far, Denisova DNA has been found in East Asians as well as indigenous people from Papua New Guinea and Australia. Therefore, it is believed that Denisova man lived in Siberia and East Asia. It is well worth pointing out that the knowledge on the Denisovan anatomy is still limited and the question of them being a separate species remains disputed, and that this means that given problem continues to be discussed within genetic relationships between prehistoric and present day humans. It is obvious that modern science still has more questions than answers when studying the Denisova man.

This study presents an exceptional collection of 54 Late Pleistocene human remains that correspond to at least three Neanderthal individuals from Simanya Gran, the main gallery of Cova Simanya, located in the northeastern Iberian Peninsula. The collection comprised 53 unpublished remains that were unearthed during the 1970s and an additional tooth discovered during 2021 excavations. The specimens represent an adult with a small stature, a periadolescent aged approximately 11.5 years, and an immature individual aged approximately 7.7 years, thus offering a more complete demographic perspective. The collection encompasses diverse anatomical parts including upper and lower dentition, mandible, vertebrae, and limb bones from both the upper and lower extremities. Attempts to extract aDNA were unsuccessful. Renewed archaeological investigations at Cova Simanya have facilitated the reevaluation of the original stratigraphic context of these remains, leading to the discovery of the additional tooth, aligning with the periadolescent individual. This assemblage is currently the most extensive Neanderthal collection from the northeastern Mediterranean Iberia, offering invaluable insights into the morphology and evolutionary trajectory of Late Pleistocene hominins. Hence, Simanya Neanderthals will enhance our understanding of Neanderthal demographics and evolution, paving the way for an in-depth examination of the morphological diversity and evolutionary context of Iberian Neanderthals.

During the Late Pleistocene, stadial and interstadial fluctuations affected vegetation, fauna, and human groups that were forced to cope with these pronounced climatic and environmental changes in time and space. These changes were especially abrupt during the Marine Isotopic Stage (MIS) 3. However, little is still known about the local and regional climatic conditions experienced by hominins in Europe. Here we reconstruct the climatic trends in northern Iberia considering the stable isotopic composition of ungulate skeletal tissues found in archaeological deposits dated between 80 to 15,000 cal BP. The carbon and oxygen isotopic composition preserved in the carbonate fraction of tooth enamel provides a reliable and high-resolution proxy of the food and water consumed by these animals, which is indirectly related to the local vegetation, environment, and climate, allowing us to estimate paleotemperatures and rainfall data. This study presents 44 bovine, equid, and cervid teeth from five archaeological sites in the Vasco-Cantabrian region (El Castillo, El Otero, Axlor, Labeko Koba, Aitzbitarte III) and one in the Mediterranean area (Canyars), where human evidence is attested from the Mousterian to the Magdalenian. The carbon isotope values reflect animals feeding on C3 plants with a mix-feeder diet mainly developed in open environments. However, carbon isotope value ranges point to differentiated ecological niches for equids and bovines, especially during the Aurignacian in the Vasco-Cantabrian region. Temperature estimations based on oxygen isotopic compositions and rainfall obtained from carbon isotopic compositions indicate colder and more arid conditions than nowadays from the Late Mousterian to the Aurignacian. The contemporary Mediterranean site shows slightly lower temperatures related to an arid period when animals mainly graze in open landscapes. In the Vasco-Cantabrian region, during the MIS2, the Gravettian data reflect a landscape opening, whereas the Magdalenian point to warmer conditions but still arid. [ABSTRACT FROM AUTHOR]

Hominins emerging from Africa in the Pleistocene required sources of vitamins in addition to sources of energy and nutrient substance (carbohydrates, proteins, and fats). Most of their vitamin requirements could be provided by eating the flesh of herbivores but vitamin C is in low concentrations in animal muscle tissue. Lack of vitamin C causes the fatal disease of scurvy. In southern Eurasia, hominins would have been able to harvest fruits and vegetables throughout the year but as they migrated further to the north, they would encounter regions in which no plants were growing in mid-winter. Vitamin C is enriched in organ meats but their mass was probably too low for adequate provision. Storage of summer crops of fruit was possible. Hominins could however fulfil ascorbic acid requirements by drinking aqueous extracts from the needles of pines and other conifers which contain adequate amounts of vitamin C to satisfy human needs. Evidence is shown of pine needle and related consumption in Paleolithic sites. [ABSTRACT FROM AUTHOR]

The cave site of Axlor (Biscay, Spain) preserves one of the most informative Middle Palaeolithic (MP) records for the North Atlantic Iberian region, though its age remains poorly known. Here we use single‐grain optically stimulated luminescence (OSL) and single‐grain thermally transferred OSL (TT‐OSL) dating of sediments to improve the age constraint of Axlor's MP succession (levels N–B). Our new ages are consistent with the previously published terminus ante quem14C ages for the site (>42.9 cal ka bp), and suggest the sequence accumulated during a period of ~50 kyr. Axlor's levels N–F were deposited ~100–80 ka, probably during marine isotope stage (MIS) 5d–a, while levels D and B were deposited ~70 and ~50 ka, respectively, during MIS 4 and mid‐MIS 3. Our results indicate that major faunal and technological turnovers occurred towards the end of MIS 5, potentially coinciding with broader environmental and climatic changes. Axlor's Quina record, dated here to the onset of MIS 4, is one of the oldest in Europe. Comparisons with neighbouring sites point to complex regional chronologies and development for this particular behaviour, though detailed correlations with other MP sequences remain difficult due to their poor chronological attributes. The present study highlights the important role that single‐grain optical dating can play in elucidating the broader evolution of the MP across southwestern Europe. [ABSTRACT FROM AUTHOR]

Ever since the availability of genomes from Neanderthals, Denisovans, and ancient humans, the field of evolutionary genomics has been searching for protein-coding variants that may hold clues to how our species evolved over the last ∼600,000 years. In this study, we identify such variants in the human-specific NOTCH2NL gene family, which were recently identified as possible contributors to the evolutionary expansion of the human brain. We find evidence for the existence of unique protein-coding NOTCH2NL variants in Neanderthals and Denisovans which could affect their ability to activate Notch signaling. Furthermore, in the Neanderthal and Denisovan genomes, we find unusual NOTCH2NL configurations, not found in any of the modern human genomes analyzed. Finally, genetic analysis of archaic and modern humans reveals ongoing adaptive evolution of modern human NOTCH2NL genes, identifying three structural variants acting complementary to drive our genome to produce a lower dosage of NOTCH2NL protein. Because copy-number variations of the 1q21.1 locus, encompassing NOTCH2NL genes, are associated with severe neurological disorders, this seemingly contradicting drive toward low levels of NOTCH2NL protein indicates that the optimal dosage of NOTCH2NL may have not yet been settled in the human population.

Human-specific pseudogenization of the CMAH gene eliminated the mammalian sialic acid (Sia) Neu5Gc (generating an excess of its precursor Neu5Ac), thus changing ubiquitous cell surface "self-associated molecular patterns" that modulate innate immunity via engagement of CD33-related-Siglec receptors. The Alu-fusion-mediated loss-of-function of CMAH fixed ∼2-3 Ma, possibly contributing to the origins of the genus Homo. The mutation likely altered human self-associated molecular patterns, triggering multiple events, including emergence of human-adapted pathogens with strong preference for Neu5Ac recognition and/or presenting Neu5Ac-containing molecular mimics of human glycans, which can suppress immune responses via CD33-related-Siglec engagement. Human-specific alterations reported in some gene-encoding Sia-sensing proteins suggested a "hotspot" in hominin evolution. The availability of more hominid genomes including those of two extinct hominins now allows full reanalysis and evolutionary timing. Functional changes occur in 8/13 members of the human genomic cluster encoding CD33-related Siglecs, all predating the human common ancestor. Comparisons with great ape genomes indicate that these changes are unique to hominins. We found no evidence for strong selection after the Human-Neanderthal/Denisovan common ancestor, and these extinct hominin genomes include almost all major changes found in humans, indicating that these changes in hominin sialobiology predate the Neanderthal-human divergence ∼0.6 Ma. Multiple changes in this genomic cluster may also explain human-specific expression of CD33rSiglecs in unexpected locations such as amnion, placental trophoblast, pancreatic islets, ovarian fibroblasts, microglia, Natural Killer(NK) cells, and epithelia. Taken together, our data suggest that innate immune interactions with pathogens markedly altered hominin Siglec biology between 0.6 and 2 Ma, potentially affecting human evolution.

Abstract Background Neanderthal introgressed DNA has been linked to different normal and disease traits including immunity and metabolism—two important functions that are altered in liver cancer. However, there is limited understanding of the relationship between Neanderthal introgression and liver cancer risk. The aim of this study was to investigate the relationship between Neanderthal introgression and liver cancer risk. Methods Using germline and somatic DNA and tumor RNA from liver cancer patients from The Cancer Genome Atlas, along with ancestry-match germline DNA from unaffected individuals from the 1000 Genomes Resource, and allele specific expression data from normal liver tissue from The Genotype-Tissue Expression project we investigated whether Neanderthal introgression impacts cancer etiology. Using a previously generated set of Neanderthal alleles, we identified Neanderthal introgressed haplotypes. We then tested whether somatic mutations are enriched or depleted on Neanderthal introgressed haplotypes compared to modern haplotypes. We also computationally assessed whether somatic mutations have a functional effect or show evidence of regulating expression of Neanderthal haplotypes. Finally, we compared patterns of Neanderthal introgression in liver cancer patients and the general population. Results We find Neanderthal introgressed haplotypes exhibit an excess of somatic mutations compared to modern haplotypes. Variant Effect Predictor analysis revealed that most of the somatic mutations on these Neanderthal introgressed haplotypes are not functional. We did observe expression differences of Neanderthal alleles between tumor and normal for four genes that also showed a pattern of enrichment of somatic mutations on Neanderthal haplotypes. However, gene expression was similar between liver cancer patients with modern ancestry and liver cancer patients with Neanderthal ancestry at these genes. Provocatively, when analyzing all genes, we find evidence of Neanderthal introgression regulating expression in tumor from liver cancer patients in two genes, ARK1C4 and OAS1. Finally, we find that most genes do not show a difference in the proportion of Neanderthal introgression between liver cancer patients and the general population. Conclusion Our results suggest that Neanderthal introgression provides opportunity for somatic mutations to accumulate, and that some Neanderthal introgression may impact liver cancer risk.

Saint-Marcel Cave, in the terminal part of the Ardèche Gorge, is a vast karstic network, and also a key Mousterian site close to the Rhône Valley. Numerous occupations dated between the last interglacial (MIS 5e) and the end of MIS 3/beginning of MIS 2 are well documented beneath the natural porch. Recently, two discoveries of Mousterian lithic industries in the entrance gallery, 150 and 500 m from the porch, have been uncovered. They attest to deep incursions by Neanderthals into very large galleries in the karst network, at considerable distances from the daylight zone. The association of these lithic industries with Pleistocene faunal assemblages, mainly from cave bear dens, suggests that Neanderthals exploited Ursidae. These discoveries thus provide new data for understanding how these hominids adapted their subsistence economy or symbolic practices to the underground environment. Neanderthal's use and frequentation of karst networks has long been ignored due to the lack of incontrovertible evidence. The discovery of Neanderthal activity in the deep network of Bruniquel Cave (France) around -170 000 years ago shed new light on our perception of the relationship between these hominids and the underground world. The multiplication of examples of Neanderthal consumption activities and raw material exploitation (skin, bones) of large carnivores, and in particular bears, gives us fresh insights into the diversity of the behavior of these hominids and their organization. In Europe, many sites have yielded such evidence. The exploitation of large carnivores by Neanderthal thus seems much less marginal than it appeared until recently. [ABSTRACT FROM AUTHOR]

Objectives: The Neanderthal patella differs from that of extant humans by being thicker anteroposteriorly and by having more symmetric medial and lateral articular facets. However, it is still unclear to what extent these differences affect knee kinesiology. We aim at assessing the endostructural conformation of Neanderthal patellae to reveal functionally related mechanical information comparatively to the extant human condition. In principle, we expect that the Neanderthal patella (i) shows a higher amount of cortical bone and (ii) a trabecular network organization distinct from the extant human condition. Materials and Methods: By using micro‐focus X‐ray tomography, we characterized the endostructure of six adult patellae from the OIS 5e Neanderthal site of Krapina, Croatia, the largest assemblage of human fossil patellae assessed so far, and compared their pattern to the configuration displayed by a sample of 22 recent humans. Results and Discussion: The first expectation is rejected, indicating that the patellar bone might have not followed the trend of generalized gracilization of the human postcranial skeleton occurred through the Upper Pleistocene. The second prediction is at least partially supported. In Krapina the trabecular network differs from the comparative sample by showing a higher medial density and by lacking a proximal reinforcement. Such conformation indicates similar load patterns exerted in Neanderthals and extant humans by the vastus lateralis, but not by the vastus medialis, with implications on the mediolateral stabilization of the knee joint. However, the patterns of structural variation of the patellar network remain to be assessed in other Neanderthal samples. [ABSTRACT FROM AUTHOR]

Spatial analysis has been much used to examine the distribution of archaeological remains at Pleistocene sites. However, little is known about the distribution patterns at sites identified as hunting camps, i.e., places occupied over multiple short periods for the capture of animals later transported to a base camp. The present work examines a Neanderthal hunting camp (the Navalmaíllo Rock Shelter in Pinilla del Valle, Madrid, Spain) to determine whether different activities were undertaken in different areas of the site. A spatial pattern was detected with a main cluster of materials (lithic tools, faunal remains, and coprolites) clearly related to the presence of nearby hearths—the backbone of the utilised space. This main cluster appears to have been related to collaborative and repetitive activities undertaken by the hunting parties that used the site. Spatial analysis also detected a small, isolated area perhaps related to carcasses processing at some point in time and another slightly altered by water. [ABSTRACT FROM AUTHOR]

The Nobel Assembly at Karolinska Institutet awarded the 2022 Nobel Prize in Physiology or Medicine to a Swedish geneticist, Svante Pääbo, for his discoveries concerning the genomes of extinct hominins and human evolution, for the sequencing of the genome of the Neanderthal, the discovery of a previously unknown hominin, Denisova, and the establishment of a new scientific discipline, paleogenomics. [ABSTRACT FROM AUTHOR]

Despite critical roles in chromosome segregation and disease, the repetitive structure and vast size of centromeres and their surrounding heterochromatic regions impede studies of genomic variation. Here we report the identification of large-scale haplotypes (cenhaps) in humans that span the centromere-proximal regions of all metacentric chromosomes, including the arrays of highly repeated α-satellites on which centromeres form. Cenhaps reveal deep diversity, including entire introgressed Neanderthal centromeres and equally ancient lineages among Africans. These centromere-spanning haplotypes contain variants, including large differences in α-satellite DNA content, which may influence the fidelity and bias of chromosome transmission. The discovery of cenhaps creates new opportunities to investigate their contribution to phenotypic variation, especially in meiosis and mitosis, as well as to more incisively model the unexpectedly rich evolution of these challenging genomic regions.

Humans are thought to be more susceptible to neurodegeneration than equivalently-aged primates. It is not known whether this vulnerability is specific to anatomically-modern humans or shared with other hominids. The contribution of introgressed Neanderthal DNA to neurodegenerative disorders remains uncertain. It is also unclear how common variants associated with neurodegenerative disease risk are maintained by natural selection in the population despite their deleterious effects. In this study, we aimed to quantify the genome-wide contribution of Neanderthal introgression and positive selection to the heritability of complex neurodegenerative disorders to address these questions.We used stratified-linkage disequilibrium score regression to investigate the relationship between five SNP-based signatures of natural selection, reflecting different timepoints of evolution, and genome-wide associated variants of the three most prevalent neurodegenerative disorders: Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease.We found no evidence for enrichment of positively-selected SNPs in the heritability of Alzheimer's disease, amyotrophic lateral sclerosis and Parkinson's disease, suggesting that common deleterious disease variants are unlikely to be maintained by positive selection. There was no enrichment of Neanderthal introgression in the SNP-heritability of these disorders, suggesting that Neanderthal admixture is unlikely to have contributed to disease risk.These findings provide insight into the origins of neurodegenerative disorders within the evolution of Homo sapiens and addresses a long-standing debate, showing that Neanderthal admixture is unlikely to have contributed to common genetic risk of neurodegeneration in anatomically-modern humans.

The consensus of creationist opinion places Homo heidelbergensis within the human holobaramin. This is based on morphological data, but what do the molecular data say? Can we build a stronger holistic case for this fossil by adding molecular data? Further evidence for the humanity of Homo heidelbergensis comes from the sequence analysis of the mitochondrial genome of several dozen primate species. Nuclear data has also been isolated from Homo heidelbergensis fossils from Sima de los Huesos. These sequencing reads and sequencing data from an archaic ("Paleolithic") human were mapped to the genomes of modern human, Neanderthal, and chimpanzee. Based on the proportion of mapping reads and the sequence similarity of these reads when mapped to the human genome, Homo heidelbergensis can confidently be placed in the human holobaramin. Both morphological and genetic evidence additively support this conclusion. [ABSTRACT FROM AUTHOR]

A few months after its publication, my friend Naoyuki Takahata presented me with a copy of the book he had written with Jan Klein. The cover of the book was most unusual. It was the reproduction of a portion of the painting of Paul Gauguin's masterpiece, now in the Museum of Fine Arts in Boston, "D'oú Venons-Nous? Que Sommes-Nous? Où Allons-Nous?" ("Where Do We Come From? What Are We? Where Are We Going?"), painted in Tahiti in 1897, six years before his tragic death. Gauguin's painting (which, interestingly, has to be viewed from right to left) depicts the spectrum of human activity from birth to death. Klein and Takahata titled their book Where Do We Come From? The Molecular Evidence for Human Descent, which I reviewed in Current Science (10 September 2002). [ABSTRACT FROM AUTHOR]

The Cioarei- Boroșteni Cave (Peștișani commune, Gorj County) is the only Mousterian site in Romania where evidence of the Neanderthal’s symbolism has been attested. Such pieces of evidence include the presence of ochre, of stone vessels for the preparation of ochre, a geode with traces of paint on its surface as well as bear skulls deposited in such a way that they may be interpreted as proof of the cave bear skull cult practised by Neanderthals. [ABSTRACT FROM AUTHOR]

Advances in contemporary genetic science have reshaped the narratives whereby individuals and communities make sense of their personal, family, and communal histories. In this process, unknown connections have been revealed and familiar orthodoxies disrupted. This essay examines the consequences of a particularly unusual revelation--the dawning awareness of the presence of nonhuman and archaic human DNA in human genetic lines--for efforts at writing about identity and society. In this autoethnographic account, I examine my own genetic inheritance of Neanderthal DNA, and posit a performative concept of genetic life writing that begins to unpack the complexities of this new knowledge about our human condition. Rather than providing the key to unlocking an "essential" humanity, the murky, messy, and multispecies genome reveals an essentially ecological quality to humanity, and to our individual identities. [ABSTRACT FROM AUTHOR]

Background: Neanderthal introgressed DNA has been linked to different normal and disease traits including immunity and metabolism—two important functions that are altered in liver cancer. However, there is limited understanding of the relationship between Neanderthal introgression and liver cancer risk. The aim of this study was to investigate the relationship between Neanderthal introgression and liver cancer risk. Methods: Using germline and somatic DNA and tumor RNA from liver cancer patients from The Cancer Genome Atlas, along with ancestry-match germline DNA from unaffected individuals from the 1000 Genomes Resource, and allele specific expression data from normal liver tissue from The Genotype-Tissue Expression project we investigated whether Neanderthal introgression impacts cancer etiology. Using a previously generated set of Neanderthal alleles, we identified Neanderthal introgressed haplotypes. We then tested whether somatic mutations are enriched or depleted on Neanderthal introgressed haplotypes compared to modern haplotypes. We also computationally assessed whether somatic mutations have a functional effect or show evidence of regulating expression of Neanderthal haplotypes. Finally, we compared patterns of Neanderthal introgression in liver cancer patients and the general population. Results: We find Neanderthal introgressed haplotypes exhibit an excess of somatic mutations compared to modern haplotypes. Variant Effect Predictor analysis revealed that most of the somatic mutations on these Neanderthal introgressed haplotypes are not functional. We did observe expression differences of Neanderthal alleles between tumor and normal for four genes that also showed a pattern of enrichment of somatic mutations on Neanderthal haplotypes. However, gene expression was similar between liver cancer patients with modern ancestry and liver cancer patients with Neanderthal ancestry at these genes. Provocatively, when analyzing all genes, we find evidence of Neanderthal introgression regulating expression in tumor from liver cancer patients in two genes, ARK1C4 and OAS1. Finally, we find that most genes do not show a difference in the proportion of Neanderthal introgression between liver cancer patients and the general population. Conclusion: Our results suggest that Neanderthal introgression provides opportunity for somatic mutations to accumulate, and that some Neanderthal introgression may impact liver cancer risk. [ABSTRACT FROM AUTHOR]

Neanderthal extinction is a matter of intense debate. It has been suggested that demography (as opposed to environment or competition) could alone provide a sufficient explanation for the phenomenon. We argue that demography cannot be a ‘stand-alone’ or ‘alternative’ explanation of token extinctions as demographic features are entangled with competitive and environmental factors, and further because demography should not be conflated with neutrality. [ABSTRACT FROM AUTHOR]

During the MIS 4 in Southwestern France, Quina Neanderthal from the north of the Aquitaine was characterized by a hunting specialization on the reindeer and the lack of diversity in their diet. They developed task-specific locations dedicated to the capture, the butchery, and the consumption of reindeer, and the whole society seems, in this region, to be dependent on this food resource. In this context, the site of Chez-Pinaud at Jonzac (France) occupies a specific place. First, interpreted as a reindeer kill and butchery site, the recent recovery of the site underlines the importance of the large ungulate (horse and bison) to the faunal spectrum (30% of the NISP). Considering the quantity of meat and grease that these species can provide to hunters, the new zooarchaeological analyses suggest that at least the horse may have played a major role in the diet of the Neanderthal population. Since Jonzac is one of the largest sites for this period, these results relativize the importance of reindeer specialization of the Quina population and the lack of diversityl in their diet.

Recent studies have reported evidence suggesting that portions of contemporary human genomes introgressed from archaic hominin populations went to high frequencies due to positive selection. However, no study to date has specifically addressed the postintrogression population dynamics of these putative cases of adaptive introgression. Here, for the first time, we specifically define cases of immediate adaptive introgression (iAI) in which archaic haplotypes rose to high frequencies in humans as a result of a selective sweep that occurred shortly after the introgression event. We define these cases as distinct from instances of selection on standing introgressed variation (SI), in which an introgressed haplotype initially segregated neutrally and subsequently underwent positive selection. Using a geographically diverse data set, we report novel cases of selection on introgressed variation in living humans and shortlist among these cases those whose selective sweeps are more consistent with having been the product of iAI rather than SI. Many of these novel inferred iAI haplotypes have potential biological relevance, including three that contain immune-related genes in West Siberians, South Asians, and West Eurasians. Overall, our results suggest that iAI may not represent the full picture of positive selection on archaically introgressed haplotypes in humans and that more work needs to be done to analyze the role of SI in the archaic introgression landscape of living humans.