Some present-day humans derive up to ∼5% 1 of their ancestry from archaic Denisovans, an even larger proportion than the ∼2% from Neanderthals 2. We developed methods that can disambiguate the ...locations of segments of Denisovan and Neanderthal ancestry in present-day humans and applied them to 257 high-coverage genomes from 120 diverse populations, among which were 20 individual Oceanians with high Denisovan ancestry 3. In Oceanians, the average size of Denisovan fragments is larger than Neanderthal fragments, implying a more recent average date of Denisovan admixture in the history of these populations (p = 0.00004). We document more Denisovan ancestry in South Asia than is expected based on existing models of history, reflecting a previously undocumented mixture related to archaic humans (p = 0.0013). Denisovan ancestry, just like Neanderthal ancestry, has been deleterious on a modern human genetic background, as reflected by its depletion near genes. Finally, the reduction of both archaic ancestries is especially pronounced on chromosome X and near genes more highly expressed in testes than other tissues (p = 1.2 × 10−7 to 3.2 × 10−7 for Denisovan and 2.2 × 10−3 to 2.9 × 10−3 for Neanderthal ancestry even after controlling for differences in level of selective constraint across gene classes). This suggests that reduced male fertility may be a general feature of mixtures of human populations diverged by >500,000 years.
•Denisovan admixture into modern humans occurred after Neanderthal admixture•There is more Denisovan ancestry in South Asians than expected from current models•Denisovan ancestry has been subject to positive and negative selection after admixture•Male infertility most likely occurred after modern human interbreeding with Denisovans
Sankararaman et al. present a map of Denisovan and Neanderthal ancestry in 120 diverse populations and show that Denisovan admixture post-dated Neanderthal admixture. South Asians have more Denisovan ancestry than expected. There was selection both for and against archaic ancestry. Hybridization with Denisovans was probably associated with reduced male fertility.
The challenge of sequencing ancient DNA has led to the development of specialized laboratory protocols that have focused on reducing contamination and maximizing the number of molecules that are ...extracted from ancient remains. Despite the fact that success in ancient DNA studies is typically obtained by screening many samples to identify a promising subset, ancient DNA protocols have not, in general, focused on reducing the time required to screen samples. We present an adaptation of a popular ancient library preparation method that makes screening more efficient. First, the DNA extract is treated using a protocol that causes characteristic ancient DNA damage to be restricted to the terminal nucleotides, while nearly eliminating it in the interior of the DNA molecules, allowing a single library to be used both to test for ancient DNA authenticity and to carry out population genetic analysis. Second, the DNA molecules are ligated to a unique pair of barcodes, which eliminates undetected cross-contamination from this step onwards. Third, the barcoded library molecules include incomplete adapters of short length that can increase the specificity of hybridization-based genomic target enrichment. The adapters are completed just before sequencing, so the same DNA library can be used in multiple experiments, and the sequences distinguished. We demonstrate this protocol on 60 ancient human samples.
Genomic studies have shown that Neanderthals interbred with modern humans, and that non-Africans today are the products of this mixture. The antiquity of Neanderthal gene flow into modern humans ...means that genomic regions that derive from Neanderthals in any one human today are usually less than a hundred kilobases in size. However, Neanderthal haplotypes are also distinctive enough that several studies have been able to detect Neanderthal ancestry at specific loci. We systematically infer Neanderthal haplotypes in the genomes of 1,004 present-day humans. Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments. We identify multiple Neanderthal-derived alleles that confer risk for disease, suggesting that Neanderthal alleles continue to shape human biology. An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals. Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes. These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.
Population mixture is an important process in biology. We present a suite of methods for learning about population mixtures, implemented in a software package called ADMIXTOOLS, that support formal ...tests for whether mixture occurred and make it possible to infer proportions and dates of mixture. We also describe the development of a new single nucleotide polymorphism (SNP) array consisting of 629,433 sites with clearly documented ascertainment that was specifically designed for population genetic analyses and that we genotyped in 934 individuals from 53 diverse populations. To illustrate the methods, we give a number of examples that provide new insights about the history of human admixture. The most striking finding is a clear signal of admixture into northern Europe, with one ancestral population related to present-day Basques and Sardinians and the other related to present-day populations of northeast Asia and the Americas. This likely reflects a history of admixture between Neolithic migrants and the indigenous Mesolithic population of Europe, consistent with recent analyses of ancient bones from Sweden and the sequencing of the genome of the Tyrolean "Iceman."
Genetic studies have consistently indicated a single common origin of Native American groups from Central and South America. However, some morphological studies have suggested a more complex picture, ...whereby the northeast Asian affinities of present-day Native Americans contrast with a distinctive morphology seen in some of the earliest American skeletons, which share traits with present-day Australasians (indigenous groups in Australia, Melanesia, and island Southeast Asia). Here we analyse genome-wide data to show that some Amazonian Native Americans descend partly from a Native American founding population that carried ancestry more closely related to indigenous Australians, New Guineans and Andaman Islanders than to any present-day Eurasians or Native Americans. This signature is not present to the same extent, or at all, in present-day Northern and Central Americans or in a ∼12,600-year-old Clovis-associated genome, suggesting a more diverse set of founding populations of the Americas than previously accepted.
We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost 400,000 polymorphisms. Enrichment of these ...positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of Western and Far Eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ∼8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ∼24,000-year-old Siberian. By ∼6,000-5,000 years ago, farmers throughout much of Europe had more hunter-gatherer ancestry than their predecessors, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but also from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ∼4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ∼75% of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ∼3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for a steppe origin of at least some of the Indo-European languages of Europe.
We report a method called ContamLD for estimating autosomal ancient DNA (aDNA) contamination by measuring the breakdown of linkage disequilibrium in a sequenced individual due to the introduction of ...contaminant DNA. ContamLD leverages the idea that contaminants should have haplotypes uncorrelated to those of the studied individual. Using simulated data, we confirm that ContamLD accurately infers contamination rates with low standard errors: for example, less than 1.5% standard error in cases with less than 10% contamination and 500,000 sequences covering SNPs. This method is optimized for application to aDNA, taking advantage of characteristic aDNA damage patterns to provide calibrated contamination estimates, and is available at https://github.com/nathan-nakatsuka/ContamLD .
Southeast Asia is home to rich human genetic and linguistic diversity, but the details of past population movements in the region are not well known. Here, we report genome-wide ancient DNA data from ...18 Southeast Asian individuals spanning from the Neolithic period through the Iron Age (4100 to 1700 years ago). Early farmers from Man Bac in Vietnam exhibit a mixture of East Asian (southern Chinese agriculturalist) and deeply diverged eastern Eurasian (hunter-gatherer) ancestry characteristic of Austroasiatic speakers, with similar ancestry as far south as Indonesia providing evidence for an expansive initial spread of Austroasiatic languages. By the Bronze Age, in a parallel pattern to Europe, sites in Vietnam and Myanmar show close connections to present-day majority groups, reflecting substantial additional influxes of migrants.
We assembled genome-wide data from 16 prehistoric Africans. We show that the anciently divergent lineage that comprises the primary ancestry of the southern African San had a wider distribution in ...the past, contributing approximately two-thirds of the ancestry of Malawi hunter-gatherers ∼8,100–2,500 years ago and approximately one-third of the ancestry of Tanzanian hunter-gatherers ∼1,400 years ago. We document how the spread of farmers from western Africa involved complete replacement of local hunter-gatherers in some regions, and we track the spread of herders by showing that the population of a ∼3,100-year-old pastoralist from Tanzania contributed ancestry to people from northeastern to southern Africa, including a ∼1,200-year-old southern African pastoralist. The deepest diversifications of African lineages were complex, involving either repeated gene flow among geographically disparate groups or a lineage more deeply diverging than that of the San contributing more to some western African populations than to others. We finally leverage ancient genomes to document episodes of natural selection in southern African populations.
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•Genome-wide analysis of 16 African individuals who lived up to 8,100 years ago•Forager populations related to southern African San were once widespread in eastern Africa•Comparison of ancient and modern Africans reveal recent genomic adaptations•Evidence for a divergent human lineage contributing to western Africans
The prehistory of African populations is explored by genome-wide analysis of 16 human remains providing insight into ancestral lineages, admixture, and genomic adaptations.
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.
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