Comparisons of whole-genome sequences from ancient and contemporary samples have pointed to several instances of archaic admixture through interbreeding between the ancestors of modern non-Africans and now extinct hominids such as Neanderthals and Denisovans. One implication of these findings is that some adaptive features in contemporary humans may have entered the population via gene flow with archaic forms in Eurasia. Within Africa, fossil evidence suggests that anatomically modern humans (AMH) and various archaic forms coexisted for much of the last 200,000 yr; however, the absence of ancient DNA in Africa has limited our ability to make a direct comparison between archaic and modern human genomes. Here, we use statistical inference based on high coverage whole-genome data (greater than 60×) from contemporary African Pygmy hunter-gatherers as an alternative means to study the evolutionary history of the genus Homo. Using whole-genome simulations that consider demographic histories that include both isolation and gene flow with neighboring farming populations, our inference method rejects the hypothesis that the ancestors of AMH were genetically isolated in Africa, thus providing the first whole genome-level evidence of African archaic admixture. Our inferences also suggest a complex human evolutionary history in Africa, which involves at least a single admixture event from an unknown archaic population into the ancestors of AMH, likely within the last 30,000 yr.

The latter part of the last glaciation, 50,000-12,000 years ago (kya), was characterized by a rapidly changing climate, cold conditions and corresponding vegetation and faunal turnover. It also coincided with the extinction of the Neanderthals and the expansion of modern human populations. Established views of modern human superiority over Neanderthals as the cause of their extinction are under attack as recent work shows that Neanderthals were capable of behaviour that is regarded as modern. As we discuss here, the exact nature of biological and cultural interactions between Neanderthals and other human groups between 50 kya and 30 kya is currently hotly contested. The extinction of the Neanderthals, and other modern human lineages, now appears to have been a drawn-out, climate-related affair.

Neanderthals, our closest extinct relatives, lived in western Eurasia from 400,000 years ago until they went extinct around 40,000 years ago. DNA retrieved from ancient specimens revealed that Neanderthals mated with modern human contemporaries. As a consequence, introgressed Neanderthal DNA survives scattered across the human genome such that 1-4% of the genome of present-day people outside Africa are inherited from Neanderthal ancestors. Patterns of Neanderthal introgressed genomic sequences suggest that Neanderthal alleles had distinct fates in the modern human genetic background. Some Neanderthal alleles facilitated human adaptation to new environments such as novel climate conditions, UV exposure levels and pathogens, while others had deleterious consequences. Here, we review the body of work on Neanderthal introgression over the past decade. We describe how evolutionary forces shaped the genomic landscape of Neanderthal introgression and highlight the impact of introgressed alleles on human biology and phenotypic variation.

Hybridization is recognized as an important evolutionary force, but identifying and timing admixture events between divergent lineages remain a major aim of evolutionary biology. While this has traditionally been done using inferential tools on contemporary genomes, the latest advances in paleogenomics have provided a growing wealth of temporally distributed genomic data. Here, we used individual-based simulations to generate chromosome-level genomic data for a 2-population system and described temporal neutral introgression patterns under a single- and 2-pulse admixture model. We computed 6 summary statistics aiming to inform the timing and number of admixture pulses between interbreeding entities: lengths of introgressed sequences and their variance within genomes, as well as genome-wide introgression proportions and related measures. The first 2 statistics could confidently be used to infer interlineage hybridization history, peaking at the beginning and shortly after an admixture pulse. Temporal variation in introgression proportions and related statistics provided more limited insights, particularly when considering their application to ancient genomes still scant in number. Lastly, we computed these statistics on Homo sapiens paleogenomes and successfully inferred the hybridization pulse from Neanderthal that occurred approximately 40 to 60 kya. The scarce number of genomes dating from this period prevented more precise inferences, but the accumulation of paleogenomic data opens promising perspectives as our approach only requires a limited number of ancient genomes.

Neanderthal and Denisovan genomes have reshaped our understanding of archaic introgression. Yet, the limited number of archaic genomes sequenced and the reliance on unadmixed outgroups have left much of this history unresolved. We introduce TRACE, a method to identify archaic ancestry using features of ancestral recombination graphs inferred from contemporary genomes alone. Simulations show that TRACE reliably detects archaic introgression without requiring archaic genomes or unadmixed outgroups. Applied to 1000 Genomes data, TRACE recovers known Neanderthal and Denisovan introgression and reveals signals of ghost admixture from previously uncharacterized hominins in both Africans and non-Africans. Strikingly, ghost ancestry persists in Neanderthal and Denisovan ancestry deserts, challenging their interpretation as Homo sapiens-specific regions. In Oceanians, TRACE finds deep lineages enriched in Denisovan––and not Neanderthal––regions, supporting a model of super-archaic gene flow. TRACE provides a scalable framework for mapping the legacy of archaic introgression in the absence of archaic genome sequences.

The disappearance of Neanderthals remains a subject of intense debate, with competing hypotheses attributing their demise to demographic decline, environmental change, competition with Homo sapiens, or genetic assimilation. Here, we present a mathematical model demonstrating that small-scale Homo sapiens immigrations into Neanderthal populations, providing recurrent gene mixing, could have led to almost complete genetic substitution over 10,000–30,000 years. Our model, grounded in neutral species drift, does not require selective advantage or catastrophic events but shows that sustained gene flow from a demographically larger species could account for Neanderthals’ genetic absorption into modern humans within a time-frame consistent with archaeological evidence. This scenario aligns with growing evidence of interbreeding and genetic introgression through recurrent H. sapiens immigration waves, providing a parsimonious explanation for the observed patterns of Neanderthal ancestry in present-day Eurasian populations. Although other factors may have contributed to the decline of Neanderthals, our results highlight genetic admixture as a possible key mechanism driving their disappearance.

No later than ~500kya the population of Homo sapiens split into three lin¬eages of independently evolving human populations: Sapiens, Neanderthals and Den¬isovans. After several hundred thousands years, they met several times and interbred with low frequency. Evidence of coupling between them is found in fossil records of Neanderthal – Sapiens offspring (Oase 1) and Neanderthal – Denisovans (Denisova 11) offspring. Moreover, the analysis of ancient and present-day population DNA shows that there were several significant gene flows between populations. Many introgressed sequences from Denisovans and Neanderthals were identified in genomes of currently living populations. All these data, according to biological species definition, may in¬dicate that populations of H. sapiens sapiens and two extinct populations H. sapiens neanderthalensis and H. sapiens denisovensis are one species. Ontological transitions from pre-human beings to humans might have happened before the initial splitting of the Homo sapiens population or after the splitting during evolution of H. sapiens sapiens lineage in Africa. If the ensoulment of the first homo occurred in the evolving populations of H. sapiens sapiens, then occasionally mixed couples (Neanderthals – Sapiens or Denisovans – Sapiens) created relations that functioned as a family, in which children could have matured.

Neanderthals, the closest evolutionary relatives of present-day humans, had been studied mostly based on their physiological traits. In addition, with the emergence of DNA sequencing technologies, the complete Neanderthal genome has been obtained and published. With that comes studies comparing Neanderthal genomes with that of modern humans. These researches revealed Neanderthal’s influences on humans in various ways. This dissertation explores the extent of Neanderthal contributions to modern humans and their physiological influence, demonstrating that Neanderthal-derived genes can have both favorable and adverse effects on humans, depending on the mode of inheritance. Overall, this study provides valuable insights into the potential significance of studying archaic hominins in the context of human evolution and medicine.

Usually, paleoanthropology studies remains and artefacts. However, more recently, genetics offer new avenues. Information on humanisation mechanisms has been obtained from comparison with primate or archaic Homo DNA sequences. Likewise, the 1 000 Genomes Project has characterized the geographic spectrum of human genetic variation offering a basis for a genomic study of Homo sapiens phylogeny. From these studies, a model, Out of Africa, was derived. His origin is Africa, where he lived 200 000 years ago. A small fraction of the population left Africa between 50 and 100 000 years ago that have populated the rest of the world, to Europe, coastal Asia to Australia and mainland Asia to Behring Land Bridge and America. The model is supported by the decrease of genetic diversity with the distance to Eastern Africa (serial founder effect). In Europe and Asia, Homo sapiens met archaic Homo neanderthalis and H denisova. The presence of 1-3% neanderthalis sequences in modern Homo ADN indicates admixtures between these groups. Some archaic sequences are on positive selection pressure, thus suggesting that the extinct hominins might have facilitated the adaptation of H sapiens to new environments.

earliest known and reliably dated location of residence for more than a single generation and a group of individuals. Homo neanderthalensis emerged in Eurasia Prehistoric Europe refers to Europe before the start of written records, beginning in the Lower Paleolithic. As history progresses, considerable regional unevenness in cultural development emerges and grows. The region of the eastern Mediterranean is, due to its geographic proximity, greatly influenced and inspired by the classical Middle Eastern civilizations, and adopts and develops the earliest Homo sapiens arrived in Europe around 46,000 and 43,000 years ago via the Levant and entered the continent through the Danubian corridor, as the fossils at the sites of Bacho Kiro cave and Peștera cu Oase suggest. With an approximate age of 46,000 years, the Homo sapiens fossils found in Bacho Kiro cave consist of a pair of fragmented mandibles including at least one molar This site yielded the oldest known ornaments in Europe, radiocarbon dated to over 43,000 years ago. The fossils' genetic structure indicates a recent Neanderthal ancestry and the discovery of a fragment of a skull in Israel in 2008 support the notion that humans interbred with Neanderthals in the Levant. After the slow processes of the previous hundreds of thousands of years, a turbulent period of Neanderthal–Homo sapiens coexistence demonstrated that cultural evolution had replaced biological evolution as the primary force of adaptation and change in human societies. Generally small and widely dispersed fossil sites suggest that Neanderthals lived in less numerous and more socially isolated groups than Homo sapiens. Tools and Levallois points are remarkably sophisticated from the outset, but they have a slow rate of variability, and general technological inertia is noticeable during the entire fossil period. Artifacts are of utilitarian nature, and symbolic behavioral traits are undocumented before the arrival of modern humans. The Aurignacian culture, introduced by modern humans, is characterized by cut bone or antler points, fine flint blades and bladelets struck from prepared cores, rather than using crude flakes. The oldest examples and subsequent widespread tradition of prehistoric art originate from the Aurignacian. After more than 100,000 years of uniformity, around 45,000 years ago, the Neanderthal fossil record changed abruptly. The Mousterian had quickly become more versatile and was named the Chatelperronian culture, which signifies the diffusion of Aurignacian elements into Neanderthal culture. Although debated, the fact proved that Neanderthals had, to some extent, adopted the culture of modern Homo sapiens. However, the Neanderthal fossil record completely vanished after 40,000…

The worldwide expansion of modern humans (Homo sapiens) started before the extinction of Neanderthals (Homo neanderthalensis). Both species coexisted and interbred, leading to slightly higher introgression in East Asians than in Europeans. This distinct ancestry level has been argued to result from selection, but range expansions of modern humans could provide an alternative explanation. This hypothesis would lead to spatial introgression gradients, increasing with distance from the expansion source. We investigate the presence of Neanderthal introgression gradients after past human expansions by analyzing Eurasian paleogenomes. We show that the out-of-Africa expansion resulted in spatial gradients of Neanderthal ancestry that persisted through time. While keeping the same gradient orientation, the expansion of early Neolithic farmers contributed decisively to reducing the Neanderthal introgression in European populations compared to Asian populations. This is because Neolithic farmers carried less Neanderthal DNA than preceding Paleolithic hunter-gatherers. This study shows that inferences about past human population dynamics can be made from the spatiotemporal variation in archaic introgression.

Humans coexisted and interbred with other hominins which later became extinct. These archaic hominins are known to us only through fossil records and for two cases, genome sequences. Here, we engineer Neanderthal and Denisovan sequences into thousands of artificial genes to reconstruct the pre-mRNA processing patterns of these extinct populations. Of the 5,169 alleles tested in this massively parallel splicing reporter assay (MaPSy), we report 962 exonic splicing mutations that correspond to differences in exon recognition between extant and extinct hominins. Using MaPSy splicing variants, predicted splicing variants, and splicing quantitative trait loci, we show that splice-disrupting variants experienced greater purifying selection in anatomically modern humans than that in Neanderthals. Adaptively introgressed variants were enriched for moderate-effect splicing variants, consistent with positive selection for alternative spliced alleles following introgression. As particularly compelling examples, we characterized a unique tissue-specific alternative splicing variant at the adaptively introgressed innate immunity gene TLR1, as well as a unique Neanderthal introgressed alternative splicing variant in the gene HSPG2 that encodes perlecan. We further identified potentially pathogenic splicing variants found only in Neanderthals and Denisovans in genes related to sperm maturation and immunity. Finally, we found splicing variants that may contribute to variation among modern humans in total bilirubin, balding, hemoglobin levels, and lung capacity. Our findings provide unique insights into natural selection acting on splicing in human evolution and demonstrate how functional assays can be used to identify candidate causal variants underlying differences in gene regulation and phenotype.