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During the last glacial-interglacial cycle, Arctic biotas experienced substantial climatic changes, yet the nature, extent and rate of their responses are not fully understood 1-8 . Here we report a large-scale environmental DNA metagenomic study of ancient plant and mammal communities, analysing 535 permafrost and lake sediment samples from across the Arctic spanning the past 50,000 years. Furthermore, we present 1,541 contemporary plant genome assemblies that were generated as reference sequences. Our study provides several insights into the long-term dynamics of the Arctic biota at the circumpolar and regional scales. Our key findings include: (1) a relatively homogeneous steppe-tundra flora dominated the Arctic during the Last Glacial Maximum, followed by regional divergence of vegetation during the Holocene epoch; (2) certain grazing animals consistently co-occurred in space and time; (3) humans appear to have been a minor factor in driving animal distributions; (4) higher effective precipitation, as well as an increase in the proportion of wetland plants, show negative effects on animal diversity; (5) the persistence of the steppe-tundra vegetation in northern Siberia enabled the late survival of several now-extinct megafauna species, including the woolly mammoth until 3.9 ± 0.2 thousand years ago (ka) and the woolly rhinoceros until 9.8 ± 0.2 ka; and (6) phylogenetic analysis of mammoth environmental DNA reveals a previously unsampled mitochondrial lineage. Our findings highlight the power of ancient environmental metagenomics analyses to advance understanding of population histories and long-term ecological dynamics., (© 2021. The Author(s).)

In less than a decade, analyses of ancient genomes have transformed our understanding of the Indigenous peopling and population history of the Americas. These studies have shown that this history, which began in the late Pleistocene epoch and continued episodically into the Holocene epoch, was far more complex than previously thought. It is now evident that the initial dispersal involved the movement from northeast Asia of distinct and previously unknown populations, including some for whom there are no currently known descendants. The first peoples, once south of the continental ice sheets, spread widely, expanded rapidly and branched into multiple populations. Their descendants-over the next fifteen millennia-experienced varying degrees of isolation, admixture, continuity and replacement, and their genomes help to illuminate the relationships among major subgroups of Native American populations. Notably, all ancient individuals in the Americas, save for later-arriving Arctic peoples, are more closely related to contemporary Indigenous American individuals than to any other population elsewhere, which challenges the claim-which is based on anatomical evidence-that there was an early, non-Native American population in the Americas. Here we review the patterns revealed by ancient genomics that help to shed light on the past peoples who created the archaeological landscape, and together lead to deeper insights into the population and cultural history of the Americas.

Advances in the isolation and sequencing of ancient DNA have begun to reveal the population histories of both people and dogs. Over the last 10,000 y, the genetic signatures of ancient dog remains have been linked with known human dispersals in regions such as the Arctic and the remote Pacific. It is suspected, however, that this relationship has a much deeper antiquity, and that the tandem movement of people and dogs may have begun soon after the domestication of the dog from a gray wolf ancestor in the late Pleistocene. Here, by comparing population genetic results of humans and dogs from Siberia, Beringia, and North America, we show that there is a close correlation in the movement and divergences of their respective lineages. This evidence places constraints on when and where dog domestication took place. Most significantly, it suggests that dogs were domesticated in Siberia by ∼23,000 y ago, possibly while both people and wolves were isolated during the harsh climate of the Last Glacial Maximum. Dogs then accompanied the first people into the Americas and traveled with them as humans rapidly dispersed into the continent beginning ∼15,000 y ago., Competing Interests: The authors declare no competing interest.

The end of the Pleistocene in North America saw the extinction of 38 genera of mostly large mammals. As their disappearance seemingly coincided with the arrival of people in the Americas, their extinction is often attributed to human overkill, notwithstanding a dearth of archaeological evidence of human predation. Moreover, this period saw the extinction of other species, along with significant changes in many surviving taxa, suggesting a broader cause, notably, the ecological upheaval that occurred as Earth shifted from a glacial to an interglacial climate. But, overkill advocates ask, if extinctions were due to climate changes, why did these large mammals survive previous glacial-interglacial transitions, only to vanish at the one when human hunters were present? This question rests on two assumptions: that previous glacial-interglacial transitions were similar to the end of the Pleistocene, and that the large mammal genera survived unchanged over multiple such cycles. Neither is demonstrably correct. Resolving the cause of large mammal extinctions requires greater knowledge of individual species' histories and their adaptive tolerances, a fuller understanding of how past climatic and ecological changes impacted those animals and their biotic communities, and what changes occurred at the Pleistocene-Holocene boundary that might have led to those genera going extinct at that time. Then we will be able to ascertain whether the sole ecologically significant difference between previous glacial-interglacial transitions and the very last one was a human presence., Competing Interests: The author declares no competing interest.

Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas.

Studies of the peopling of the Americas have focused on the timing and number of initial migrations. Less attention has been paid to the subsequent spread of people within the Americas. We sequenced 15 ancient human genomes spanning from Alaska to Patagonia; six are ≥10,000 years old (up to ~18× coverage). All are most closely related to Native Americans, including those from an Ancient Beringian individual and two morphologically distinct "Paleoamericans." We found evidence of rapid dispersal and early diversification that included previously unknown groups as people moved south. This resulted in multiple independent, geographically uneven migrations, including one that provides clues of a Late Pleistocene Australasian genetic signal, as well as a later Mesoamerican-related expansion. These led to complex and dynamic population histories from North to South America., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Despite broad agreement that the Americas were initially populated via Beringia, the land bridge that connected far northeast Asia with northwestern North America during the Pleistocene epoch, when and how the peopling of the Americas occurred remains unresolved. Analyses of human remains from Late Pleistocene Alaska are important to resolving the timing and dispersal of these populations. The remains of two infants were recovered at Upward Sun River (USR), and have been dated to around 11.5 thousand years ago (ka). Here, by sequencing the USR1 genome to an average coverage of approximately 17 times, we show that USR1 is most closely related to Native Americans, but falls basal to all previously sequenced contemporary and ancient Native Americans. As such, USR1 represents a distinct Ancient Beringian population. Using demographic modelling, we infer that the Ancient Beringian population and ancestors of other Native Americans descended from a single founding population that initially split from East Asians around 36 ± 1.5 ka, with gene flow persisting until around 25 ± 1.1 ka. Gene flow from ancient north Eurasians into all Native Americans took place 25-20 ka, with Ancient Beringians branching off around 22-18.1 ka. Our findings support a long-term genetic structure in ancestral Native Americans, consistent with the Beringian 'standstill model'. We show that the basal northern and southern Native American branches, to which all other Native Americans belong, diverged around 17.5-14.6 ka, and that this probably occurred south of the North American ice sheets. We also show that after 11.5 ka, some of the northern Native American populations received gene flow from a Siberian population most closely related to Koryaks, but not Palaeo-Eskimos, Inuits or Kets, and that Native American gene flow into Inuits was through northern and not southern Native American groups. Our findings further suggest that the far-northern North American presence of northern Native Americans is from a back migration that replaced or absorbed the initial founding population of Ancient Beringians.

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.)

During the Last Glacial Maximum, continental ice sheets isolated Beringia (northeast Siberia and northwest North America) from unglaciated North America. By around 15 to 14 thousand calibrated radiocarbon years before present (cal. kyr bp), glacial retreat opened an approximately 1,500-km-long corridor between the ice sheets. It remains unclear when plants and animals colonized this corridor and it became biologically viable for human migration. We obtained radiocarbon dates, pollen, macrofossils and metagenomic DNA from lake sediment cores in a bottleneck portion of the corridor. We find evidence of steppe vegetation, bison and mammoth by approximately 12.6 cal. kyr bp, followed by open forest, with evidence of moose and elk at about 11.5 cal. kyr bp, and boreal forest approximately 10 cal. kyr bp. Our findings reveal that the first Americans, whether Clovis or earlier groups in unglaciated North America before 12.6 cal. kyr bp, are unlikely to have travelled by this route into the Americas. However, later groups may have used this north-south passageway.

How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericúes and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model., (Copyright © 2015, American Association for the Advancement of Science.)

Kennewick Man, referred to as the Ancient One by Native Americans, is a male human skeleton discovered in Washington state (USA) in 1996 and initially radiocarbon dated to 8,340-9,200 calibrated years before present (BP). His population affinities have been the subject of scientific debate and legal controversy. Based on an initial study of cranial morphology it was asserted that Kennewick Man was neither Native American nor closely related to the claimant Plateau tribes of the Pacific Northwest, who claimed ancestral relationship and requested repatriation under the Native American Graves Protection and Repatriation Act (NAGPRA). The morphological analysis was important to judicial decisions that Kennewick Man was not Native American and that therefore NAGPRA did not apply. Instead of repatriation, additional studies of the remains were permitted. Subsequent craniometric analysis affirmed Kennewick Man to be more closely related to circumpacific groups such as the Ainu and Polynesians than he is to modern Native Americans. In order to resolve Kennewick Man's ancestry and affiliations, we have sequenced his genome to ∼1× coverage and compared it to worldwide genomic data including for the Ainu and Polynesians. We find that Kennewick Man is closer to modern Native Americans than to any other population worldwide. Among the Native American groups for whom genome-wide data are available for comparison, several seem to be descended from a population closely related to that of Kennewick Man, including the Confederated Tribes of the Colville Reservation (Colville), one of the five tribes claiming Kennewick Man. We revisit the cranial analyses and find that, as opposed to genome-wide comparisons, it is not possible on that basis to affiliate Kennewick Man to specific contemporary groups. We therefore conclude based on genetic comparisons that Kennewick Man shows continuity with Native North Americans over at least the last eight millennia.

Purpose: We conducted a basket clinical trial to assess the feasibility of such a design strategy and to independently evaluate the effects of multiple targeted agents against specific molecular aberrations in multiple histologic subtypes concurrently., Patients and Methods: We enrolled patients with advanced non-small-cell lung cancer (NSCLC), small-cell lung cancer, and thymic malignancies who underwent genomic characterization of oncogenic drivers. Patients were enrolled onto a not-otherwise-specified arm and treated with standard-of-care therapies or one of the following five biomarker-matched treatment groups: erlotinib for EGFR mutations; selumetinib for KRAS, NRAS, HRAS, or BRAF mutations; MK2206 for PIK3CA, AKT, or PTEN mutations; lapatinib for ERBB2 mutations or amplifications; and sunitinib for KIT or PDGFRA mutations or amplification., Results: Six hundred forty-seven patients were enrolled, and 88% had their tumors tested for at least one gene. EGFR mutation frequency was 22.1% in NSCLC, and erlotinib achieved a response rate of 60% (95% CI, 32.3% to 83.7%). KRAS mutation frequency was 24.9% in NSCLC, and selumetinib failed to achieve its primary end point, with a response rate of 11% (95% CI, 0% to 48%). Completion of accrual to all other arms was not feasible. In NSCLC, patients with EGFR mutations had the longest median survival (3.51 years; 95% CI, 2.89 to 5.5 years), followed by those with ALK rearrangements (2.94 years; 95% CI, 1.66 to 4.61 years), those with KRAS mutations (2.3 years; 95% CI, 2.3 to 2.17 years), those with other genetic abnormalities (2.17 years; 95% CI, 1.3 to 2.74 years), and those without an actionable mutation (1.85 years; 95% CI, 1.61 to 2.13 years)., Conclusion: This basket trial design was not feasible for many of the arms with rare mutations, but it allowed the study of the genetics of less common malignancies., (© 2015 by American Society of Clinical Oncology.)

According to the Younger Dryas Impact Hypothesis (YDIH), ∼ 12,800 calendar years before present, North America experienced an extraterrestrial impact that triggered the Younger Dryas and devastated human populations and biotic communities on this continent and elsewhere. This supposed event is reportedly marked by multiple impact indicators, but critics have challenged this evidence, and considerable controversy now surrounds the YDIH. Proponents of the YDIH state that a key test of the hypothesis is whether those indicators are isochronous and securely dated to the Younger Dryas onset. They are not. We have examined the age basis of the supposed Younger Dryas boundary layer at the 29 sites and regions in North and South America, Europe, and the Middle East in which proponents report its occurrence. Several of the sites lack any age control, others have radiometric ages that are chronologically irrelevant, nearly a dozen have ages inferred by statistically and chronologically flawed age-depth interpolations, and in several the ages directly on the supposed impact layer are older or younger than ∼ 12,800 calendar years ago. Only 3 of the 29 sites fall within the temporal window of the YD onset as defined by YDIH proponents. The YDIH fails the critical chronological test of an isochronous event at the YD onset, which, coupled with the many published concerns about the extraterrestrial origin of the purported impact markers, renders the YDIH unsupported. There is no reason or compelling evidence to accept the claim that a cosmic impact occurred ∼ 12,800 y ago and caused the Younger Dryas.

Clovis, with its distinctive biface, blade and osseous technologies, is the oldest widespread archaeological complex defined in North America, dating from 11,100 to 10,700 (14)C years before present (bp) (13,000 to 12,600 calendar years bp). Nearly 50 years of archaeological research point to the Clovis complex as having developed south of the North American ice sheets from an ancestral technology. However, both the origins and the genetic legacy of the people who manufactured Clovis tools remain under debate. It is generally believed that these people ultimately derived from Asia and were directly related to contemporary Native Americans. An alternative, Solutrean, hypothesis posits that the Clovis predecessors emigrated from southwestern Europe during the Last Glacial Maximum. Here we report the genome sequence of a male infant (Anzick-1) recovered from the Anzick burial site in western Montana. The human bones date to 10,705 ± 35 (14)C years bp (approximately 12,707-12,556 calendar years bp) and were directly associated with Clovis tools. We sequenced the genome to an average depth of 14.4× and show that the gene flow from the Siberian Upper Palaeolithic Mal'ta population into Native American ancestors is also shared by the Anzick-1 individual and thus happened before 12,600 years bp. We also show that the Anzick-1 individual is more closely related to all indigenous American populations than to any other group. Our data are compatible with the hypothesis that Anzick-1 belonged to a population directly ancestral to many contemporary Native Americans. Finally, we find evidence of a deep divergence in Native American populations that predates the Anzick-1 individual.

Waters and Stafford (Reports, 23 February 2007, p. 1122) provided useful information about the age of some Clovis sites but have not definitively established the temporal span of this cultural complex in the Americas. Only a continuing program of radiometric dating and careful stratigraphic correlations can address the lingering ambiguity about the emergence and spread of Clovis culture.