The first decade of ancient genomics has revolutionized the study of human prehistory and evolution. We review new insights based on prehistoric modern human genomes, including greatly increased resolution of the timing and structure of the out-of-Africa expansion, the diversification of present-day non-African populations, and the earliest expansions of those populations into Eurasia and America. Prehistoric genomes now document population transformations on every inhabited continent-in particular the effect of agricultural expansions in Africa, Europe, and Oceania-and record a history of natural selection that shapes present-day phenotypic diversity. Despite these advances, much remains unknown, in particular about the genomic histories of Asia (the most populous continent) and Africa (the continent that contains the most genetic diversity). Ancient genomes from these and other regions, integrated with a growing understanding of the genomic basis of human phenotypic diversity, will be in focus during the next decade of research in the field.

Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.

We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30×) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of "missing evolution" in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.

Recent advancements in DNA sequencing technologies and laboratory preparation protocols have rapidly expanded the scope of ancient DNA research over the past decade, both temporally and geographically. Discoveries include interactions between archaic and modern humans as well as modern human population dynamics, including those coinciding with the Last Glacial Maximum and the settlement history of most world regions. This new type of data allows us to examine the deep past of human population dynamics and sharpen the current understanding of our present. The continued development in the ancient DNA field has transformed our understanding of human genetic history and will keep uncovering the further mysteries of our recent evolutionary past.

Human genetic history in East Asia is poorly understood. To clarify population relationships, we obtained genome-wide data from 26 ancient individuals from northern and southern East Asia spanning 9500 to 300 years ago. Genetic differentiation in this region was higher in the past than the present, which reflects a major episode of admixture involving northern East Asian ancestry spreading across southern East Asia after the Neolithic, thereby transforming the genetic ancestry of southern China. Mainland southern East Asian and Taiwan Strait island samples from the Neolithic show clear connections with modern and ancient individuals with Austronesian-related ancestry, which supports an origin in southern China for proto-Austronesians. Connections among Neolithic coastal groups from Siberia and Japan to Vietnam indicate that migration and gene flow played an important role in the prehistory of coastal Asia.Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

In order to resolve long-standing issues surrounding the age of the Skhul early modern humans, new analyses have been conducted, including the dating of four well-provenanced fossils by ESR and U-series. If the Skhul burials took place within a relatively short time span, then the best age estimate lies between 100 and 135 ka. This result agrees very well with TL ages obtained from burnt flint of 119+/-18 ka (Mercier et al., 1993). However, we cannot exclude the possibility that the material associated with the Skhul IX burial is older than those of Skhul II and Skhul V. These and other recent age estimates suggest that the three burial sites, Skhul, Qafzeh and Tabun are broadly contemporaneous, falling within the time range of 100 to 130 ka. The presence of early representatives of both early modern humans and Neanderthals in the Levant during Marine Isotope Stage 5 inevitably complicates attempts at segregating these populations by date or archaeological association. Nevertheless, it does appear that the oldest known symbolic burials are those of early modern humans at Skhul and Qafzeh. This supports the view that, despite the associated Middle Palaeolithic technology, elements of modern human behaviour were represented at Skhul and Qafzeh prior to 100 ka.

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.

Hominins with morphology similar to present-day humans appear in the fossil record across Eurasia between 40,000 and 50,000 y ago. The genetic relationships between these early modern humans and present-day human populations have not been established. We have extracted DNA from a 40,000-y-old anatomically modern human from Tianyuan Cave outside Beijing, China. Using a highly scalable hybridization enrichment strategy, we determined the DNA sequences of the mitochondrial genome, the entire nonrepetitive portion of chromosome 21 (∼30 Mbp), and over 3,000 polymorphic sites across the nuclear genome of this individual. The nuclear DNA sequences determined from this early modern human reveal that the Tianyuan individual derived from a population that was ancestral to many present-day Asians and Native Americans but postdated the divergence of Asians from Europeans. They also show that this individual carried proportions of DNA variants derived from archaic humans similar to present-day people in mainland Asia.

Thirty-four elements of an early modern human (EMH) were found in Tianyuan Cave, Zhoukoudian, China in 2003. Dated to 42,000–39,000 calendrical years before present by using direct accelerator mass spectrometry radiocarbon, the Tianyuan 1 skeleton is among the oldest directly dated EMHs in eastern Eurasia. Morphological comparison shows Tianyuan 1 to have a series of derived modern human characteristics, including a projecting tuber symphyseos, a high anterior symphyseal angle, a broad scapular glenoid fossa, a reduced hamulus, a gluteal buttress, and a pilaster on the femora. Other features of Tianyuan 1 that are more common among EMHs are its modest humeral pectoralis major tuberosities, anteriorly rotated radial tuberosity, reduced radial curvature, and modest talar trochlea. It also lacks several mandibular features common among western Eurasian late archaic humans, including mandibular foramen bridging, mandibular notch asymmetry, and a large superior medial pterygoid tubercle. However, Tianyuan 1 exhibits several late archaic human features, such as its anterior to posterior dental proportions, a large hamulus length, and a broad and rounded distal phalangeal tuberosity. This morphological pattern implies that a simple spread of modern humans from Africa is unlikely.

By at least 45,000 years before present, anatomically modern humans had spread across Eurasia [1-3], but it is not well known how diverse these early populations were and whether they contributed substantially to later people or represent early modern human expansions into Eurasia that left no surviving descendants today. Analyses of genome-wide data from several ancient individuals from Western Eurasia and Siberia have shown that some of these individuals have relationships to present-day Europeans [4, 5] while others did not contribute to present-day Eurasian populations [3, 6]. As contributions from Upper Paleolithic populations in Eastern Eurasia to present-day humans and their relationship to other early Eurasians is not clear, we generated genome-wide data from a 40,000-year-old individual from Tianyuan Cave, China, [1, 7] to study his relationship to ancient and present-day humans. We find that he is more related to present-day and ancient Asians than he is to Europeans, but he shares more alleles with a 35,000-year-old European individual than he shares with other ancient Europeans, indicating that the separation between early Europeans and early Asians was not a single population split. We also find that the Tianyuan individual shares more alleles with some Native American groups in South America than with Native Americans elsewhere, providing further support for population substructure in Asia [8] and suggesting that this persisted from 40,000 years ago until the colonization of the Americas. Our study of the Tianyuan individual highlights the complex migration and subdivision of early human populations in Eurasia.Copyright © 2017 Elsevier Ltd. All rights reserved.

The origin of contemporary Europeans remains contentious. We obtained a genome sequence from Kostenki 14 in European Russia dating from 38,700 to 36,200 years ago, one of the oldest fossils of anatomically modern humans from Europe. We find that Kostenki 14 shares a close ancestry with the 24,000-year-old Mal'ta boy from central Siberia, European Mesolithic hunter-gatherers, some contemporary western Siberians, and many Europeans, but not eastern Asians. Additionally, the Kostenki 14 genome shows evidence of shared ancestry with a population basal to all Eurasians that also relates to later European Neolithic farmers. We find that Kostenki 14 contains more Neandertal DNA that is contained in longer tracts than present Europeans. Our findings reveal the timing of divergence of western Eurasians and East Asians to be more than 36,200 years ago and that European genomic structure today dates back to the Upper Paleolithic and derives from a metapopulation that at times stretched from Europe to central Asia. Copyright © 2014, American Association for the Advancement of Science.

Present-day hunter-gatherers (HGs) live in multilevel social groups essential to sustain a population structure characterized by limited levels of within-band relatedness and inbreeding. When these wider social networks evolved among HGs is unknown. To investigate whether the contemporary HG strategy was already present in the Upper Paleolithic, we used complete genome sequences from Sunghir, a site dated to ~34,000 years before the present, containing multiple anatomically modern human individuals. We show that individuals at Sunghir derive from a population of small effective size, with limited kinship and levels of inbreeding similar to HG populations. Our findings suggest that Upper Paleolithic social organization was similar to that of living HGs, with limited relatedness within residential groups embedded in a larger mating network.Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

We analyzed the whole-genome sequences of a family of four, consisting of two siblings and their parents. Family-based sequencing allowed us to delineate recombination sites precisely, identify 70% of the sequencing errors (resulting in > 99.999% accuracy), and identify very rare single-nucleotide polymorphisms. We also directly estimated a human intergeneration mutation rate of approximately 1.1 x 10(-8) per position per haploid genome. Both offspring in this family have two recessive disorders: Miller syndrome, for which the gene was concurrently identified, and primary ciliary dyskinesia, for which causative genes have been previously identified. Family-based genome analysis enabled us to narrow the candidate genes for both of these Mendelian disorders to only four. Our results demonstrate the value of complete genome sequencing in families.

It is now possible to make direct measurements of the mutation rate in modern humans using next-generation sequencing. These measurements reveal a value that is approximately half of that previously derived from fossil calibration, and this has implications for our understanding of demographic events in human evolution and other aspects of population genetics. Here, we discuss the implications of a lower-than-expected mutation rate in relation to the timescale of human evolution.

High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence.

The availability of complete human genome sequences from populations across the world has given rise to new population genetic inference methods that explicitly model ancestral relationships under recombination and mutation. So far, application of these methods to evolutionary history more recent than 20,000-30,000 years ago and to population separations has been limited. Here we present a new method that overcomes these shortcomings. The multiple sequentially Markovian coalescent (MSMC) analyzes the observed pattern of mutations in multiple individuals, focusing on the first coalescence between any two individuals. Results from applying MSMC to genome sequences from nine populations across the world suggest that the genetic separation of non-African ancestors from African Yoruban ancestors started long before 50,000 years ago and give information about human population history as recent as 2,000 years ago, including the bottleneck in the peopling of the Americas and separations within Africa, East Asia and Europe.

A major topic of interest in human prehistory is how the large-scale genetic structure of modern populations outside of Africa was established. Demographic models have been developed that capture the relationships among small numbers of populations or within particular geographical regions, but constructing a phylogenetic tree with gene flow events for a wide diversity of non-Africans remains a difficult problem. Here, we report a model that provides a good statistical fit to allele-frequency correlation patterns among East Asians, Australasians, Native Americans, and ancient western and northern Eurasians, together with archaic human groups. The model features a primary eastern/western bifurcation dating to at least 45,000 years ago, with Australasians nested inside the eastern clade, and a parsimonious set of admixture events. While our results still represent a simplified picture, they provide a useful summary of deep Eurasian population history that can serve as a null model for future studies and a baseline for further discoveries.© The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

We present analyses of the genome of a ~34,000-year-old hominin skull cap discovered in the Salkhit Valley in northeastern Mongolia. We show that this individual was a female member of a modern human population that, following the split between East and West Eurasians, experienced substantial gene flow from West Eurasians. Both she and a 40,000-year-old individual from Tianyuan outside Beijing carried genomic segments of Denisovan ancestry. These segments derive from the same Denisovan admixture event(s) that contributed to present-day mainland Asians but are distinct from the Denisovan DNA segments in present-day Papuans and Aboriginal Australians.Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Neanderthals were a group of archaic hominins that occupied most of Europe and parts of Western Asia from ∼30,000 to 300,000 years ago (KYA). They coexisted with modern humans during part of this time. Previous genetic analyses that compared a draft sequence of the Neanderthal genome with genomes of several modern humans concluded that Neanderthals made a small (1-4%) contribution to the gene pools of all non-African populations. This observation was consistent with a single episode of admixture from Neanderthals into the ancestors of all non-Africans when the two groups coexisted in the Middle East 50-80 KYA. We examined the relationship between Neanderthals and modern humans in greater detail by applying two complementary methods to the published draft Neanderthal genome and an expanded set of high-coverage modern human genome sequences. We find that, consistent with the recent finding of Meyer et al. (2012), Neanderthals contributed more DNA to modern East Asians than to modern Europeans. Furthermore we find that the Maasai of East Africa have a small but significant fraction of Neanderthal DNA. Because our analysis is of several genomic samples from each modern human population considered, we are able to document the extent of variation in Neanderthal ancestry within and among populations. Our results combined with those previously published show that a more complex model of admixture between Neanderthals and modern humans is necessary to account for the different levels of Neanderthal ancestry among human populations. In particular, at least some Neanderthal-modern human admixture must postdate the separation of the ancestors of modern European and modern East Asian populations.

Early Neolithic (~7700-year-old) genetic data from the Russian Far East implies a high level of genetic continuity in this region.

\n Ancient genomes reveal a complex demographic picture since the post-LGM in northeast Asia and report the presence of\n Y. pestis\n.\n

Modern humans have inhabited the Lake Baikal region since the Upper Paleolithic, though the precise history of its peoples over this long time span is still largely unknown. Here, we report genome-wide data from 19 Upper Paleolithic to Early Bronze Age individuals from this Siberian region. An Upper Paleolithic genome shows a direct link with the First Americans by sharing the admixed ancestry that gave rise to all non-Arctic Native Americans. We also demonstrate the formation of Early Neolithic and Bronze Age Baikal populations as the result of prolonged admixture throughout the eighth to sixth millennium BP. Moreover, we detect genetic interactions with western Eurasian steppe populations and reconstruct Yersinia pestis genomes from two Early Bronze Age individuals without western Eurasian ancestry. Overall, our study demonstrates the most deeply divergent connection between Upper Paleolithic Siberians and the First Americans and reveals human and pathogen mobility across Eurasia during the Bronze Age.Copyright © 2020 Elsevier Inc. All rights reserved.

The human occupation history of Southeast Asia (SEA) remains heavily debated. Current evidence suggests that SEA was occupied by Hòabìnhian hunter-gatherers until ~4000 years ago, when farming economies developed and expanded, restricting foraging groups to remote habitats. Some argue that agricultural development was indigenous; others favor the "two-layer" hypothesis that posits a southward expansion of farmers giving rise to present-day Southeast Asian genetic diversity. By sequencing 26 ancient human genomes (25 from SEA, 1 Japanese Jōmon), we show that neither interpretation fits the complexity of Southeast Asian history: Both Hòabìnhian hunter-gatherers and East Asian farmers contributed to current Southeast Asian diversity, with further migrations affecting island SEA and Vietnam. Our results help resolve one of the long-standing controversies in Southeast Asian prehistory.Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

\n The Eurasian steppes reach from the Ukraine in Europe to Mongolia and China. Over the past 5000 years, these flat grasslands were thought to be the route for the ebb and flow of migrant humans, their horses, and their languages. de Barros Damgaard\n et al.\n probed whole-genome sequences from the remains of 74 individuals found across this region. Although there is evidence for migration into Europe from the steppes, the details of human movements are complex and involve independent acquisitions of horse cultures. Furthermore, it appears that the Indo-European Hittite language derived from Anatolia, not the steppes. The steppe people seem not to have penetrated South Asia. Genetic evidence indicates an independent history involving western Eurasian admixture into ancient South Asian peoples.\n

Jones, Eppie R.; Martiniano, Rui; McLaughlin, Russell L.; Cassidy, Lara M.; Gamba, Cristina; Pinhasi, Ron; Bradley, Daniel G. Univ Dublin Trinity Coll, Smurfit Inst Genet, Dublin 2, Ireland. Gonzalez-Fortes, Gloria; Hofreiter, Michael Univ Potsdam, Inst Biochem & Biol, Dept Math & Nat Sci, D-14476 Potsdam, Germany. Gonzalez-Fortes, Gloria Univ Ferrara, Dept Biol & Evolut, I-44100 Ferrara, Italy. Connell, Sarah; Gamba, Cristina; Pinhasi, Ron Univ Coll Dublin, Sch Archaeol, Dublin 4, Ireland. Connell, Sarah; Gamba, Cristina; Pinhasi, Ron Univ Coll Dublin, Earth Inst, Dublin 4, Ireland. Siska, Veronika; Eriksson, Anders; Llorente, Marcos Gallego; Manica, Andrea Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England. Eriksson, Anders King Abdullah Univ Sci & Technol, Div Biol & Environm Sci & Engn, Integrat Syst Biol Lab, Thuwal 239556900, Saudi Arabia. Gamba, Cristina Univ Copenhagen, Nat Hist Museum Denmark, Ctr GeoGenet, DK-1350 Copenhagen, Denmark. Meshveliani, Tengiz; Jakeli, Nino; Lordkipanidze, David Georgian Natl Museum, GE-0105 Tbilisi, Rep of Georgia. Bar-Yosef, Ofer Harvard Univ, Peabody Museum, Dept Anthropol, Cambridge, MA 02138 USA. Mueller, Werner Univ Neuchatel, Lab Archeozool, CH-2000 Neuchatel, Switzerland. Mueller, Werner LATENIUM, Off Patrimoine & Archeol Neuchatel, Sect Archeol, CH-2068 Hauterive, Switzerland. Belfer-Cohen, Anna Hebrew Univ Jerusalem, Inst Archaeol, IL-91905 Jerusalem, Israel. Matskevich, Zinovi Israel Antiqu Author, IL-91004 Jerusalem, Israel. Higham, Thomas F. G. Univ Oxford, Oxford Radiocarbon Accelerator Unit, Res Lab Archaeol & Hist Art, Oxford OX1 3QY, England. Currat, Mathias Univ Geneva, Anthropol Unit, Dept Genet & Evolut, Lab Anthropol Genet & Peopling Hist AGP, CH-1227 Geneva, Switzerland.

The genetic relationship of past modern humans to today's populations and each other was largely unknown until recently, when advances in ancient DNA sequencing allowed for unprecedented analysis of the genomes of these early people. These ancient genomes reveal new insights into human prehistory not always observed studying present-day populations, including greater details on the genetic diversity, population structure, and gene flow that characterized past human populations, particularly in early Eurasia, as well as increased insight on the relationship between archaic and modern humans. Here, we review genetic studies on ∼45000- to 7500-year-old individuals associated with mainly preagricultural cultures found in Eurasia, the Americas, and Africa.Copyright © 2017 Elsevier Ltd. All rights reserved.

Northern China harbored the world's earliest complex societies based on millet farming, in two major centers in the Yellow (YR) and West Liao (WLR) River basins. Until now, their genetic histories have remained largely unknown. Here we present 55 ancient genomes dating to 7500-1700 BP from the YR, WLR, and Amur River (AR) regions. Contrary to the genetic stability in the AR, the YR and WLR genetic profiles substantially changed over time. The YR populations show a monotonic increase over time in their genetic affinity with present-day southern Chinese and Southeast Asians. In the WLR, intensification of farming in the Late Neolithic is correlated with increased YR affinity while the inclusion of a pastoral economy in the Bronze Age was correlated with increased AR affinity. Our results suggest a link between changes in subsistence strategy and human migration, and fuel the debate about archaeolinguistic signatures of past human migration.