The history of click-speaking Khoe-San, and African populations in general, remains poorly understood. We genotyped ∼2.3 million SNPs in 220 southern Africans and found that the Khoe-San diverged from other populations ≥100,000 years ago, but structure within the Khoe-San dated back to about 35,000 years ago. Genetic variation in various sub-Saharan populations did not localize the origin of modern humans to a single geographic region within Africa; instead, it indicated a history of admixture and stratification. We found evidence of adaptation targeting muscle function and immune response, potential adaptive introgression of UV-light protection, and selection predating modern human diversification involving skeletal and neurological development. These new findings illustrate the importance of African genomic diversity in understanding human evolutionary history.

Recent studies of ancient genomes have suggested that gene flow from archaic hominin groups to the ancestors of modern humans occurred on two separate occasions during the modern human expansion out of Africa. At the same time, decreasing levels of human genetic diversity have been found at increasing distance from Africa as a consequence of human expansion out of Africa. We analyzed the signal of archaic ancestry in modern human populations, and we investigated how serial founder models of human expansion affect the signal of archaic ancestry using simulations. For descendants of an archaic admixture event, we show that genetic drift coupled with ascertainment bias for common alleles can cause artificial but largely predictable differences in similarity to archaic genomes. In genotype data from non-Africans, this effect results in a biased genetic similarity to Neandertals with increasing distance from Africa. However, in addition to the previously reported gene flow between Neandertals and non-Africans as well as gene flow between an archaic human population from Siberia ("Denisovans") and Oceanians, we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisovagenome-a pattern that is not expected under a model of solely Neandertal admixture in the ancestry of East Asians. These results suggest admixture between Denisovans or a Denisova-related population and the ancestors of East Asians, and that the history of anatomically modern and archaic humans might be more complex than previously proposed.

The farming way of life originated in the Near East some 11,000 years ago and had reached most of the European continent 5000 years later. However, the impact of the agricultural revolution on demography and patterns of genomic variation in Europe remains unknown. We obtained 249 million base pairs of genomic DNA from similar to 5000-year-old remains of three hunter-gatherers and one farmer excavated in Scandinavia and find that the farmer is genetically most similar to extant southern Europeans, contrasting sharply to the hunter-gatherers, whose distinct genetic signature is most similar to that of extant northern Europeans. Our results suggest that migration from southern Europe catalyzed the spread of agriculture and that admixture in the wake of this expansion eventually shaped the genomic landscape of modern-day Europe.

Recent ancient DNA studies have provided new evidence for prehistoric population structure associated with the contentious transition to an agricultural lifestyle in Europe. In this study, we infer human population structure and history in Holocene Europe by generating ancient genomic sequence data from 9 Scandinavian individuals associated with the foraging Pitted Ware Culture and the agricultural Funnel Beaker Culture (TRB). We obtained up to 1.1x coverage of the genomes for the nine individuals allowing direct comparisons of the two groups. We show that the Neolithic Scandinavian individuals show remarkable population structure corresponding to their cultural association. Looking beyond Scandinavia, we integrate this data with ancient genomes from Southern Europe and find that the Tyrolean Iceman from an agricultural context is most similar to Scandinavian individuals from a farming context, whereas Mesolithic Iberian hunter-gatherers are most similar to Scandinavian hunter-gatherers, opposite to what would have been predicted from their geographical origins. This finding shows that among these individuals, lifestyle is the major determinant of genetic ancestry rather than geography. Comparisons with modern populations reveal a latitudinal relationship where Southern European populations such as Sardinians are closely related with the genetic variation of the agricultural groups, whereas hunter-gatherer individuals appear to have the closest relationship with Baltic populations such as Lithuanians and present-day Scandinavians. Our results also demonstrate that while Middle Eastern populations are not the most similar to Neolithic farmers, this observation can be explained by African-related admixture in more recent times for Middle Eastern groups, which, once accounted for, reveals that the other major component of their ancestry resembles Neolithic farmers. While present-day Scandinavian populations are intermediate between the two groups, consistent with admixture, they appear genetically slightly closer to Neolithic hunter-gatherers than Neolithic farmers. This suggests a model where initial colonization by agricultural populations was followed by later admixture with hunter-gatherer populations or gene flow from other regions.

One of the main impediments for obtaining DNA sequences from ancient humanskeletons is the presence of contaminating modern human DNA molecules in many fossil samples and laboratory reagents. However, DNA fragments isolated from ancient specimens show a characteristic DNA damage pattern, caused by miscoding lesions, that differs from present-day DNA sequences. Here, we develop a framework for evaluating the likelihood of a sequence originating from a model with post-mortem degradation (PMD)—summarized in a PMD score—which allows the identification of DNA fragments that are unlikely to originate from present-day sources. We apply this approach to a contaminated Neandertal specimen from the Okladnikov cave in Siberia in order to isolate its endogenous DNA from modern human contaminants, and show that the reconstructed mitochondrial genome sequence is more closely related to the variation of Western Neandertals than what was discernible from previous analyses. Our method opens up the potential for genomic analysis of contaminated fossil material.

The rapid advance of sequencing technology coupled with improvements in molecular methods for obtaining genetic data from ancient sources holds the promise of producing a wealth of genomic data from time-separated individuals. However, the population genetic properties of time-structured samples have not been extensively explored. Here, we consider the implications of temporal sampling for analyses of genetic differentiation, and use a temporal coalescent framework to show that complex historical events such as size reductions, population replacements, and transient genetic barriers between populations leave a footprint of genetic differentiation that can be traced through history using temporal samples. Our results emphasize explicit consideration of the temporal structure when making inferences, and indicate that genomic data from ancient individuals will greatly increase our ability to reconstruct population history.