The indigenous people of the Tibetan Plateau have been the subject of much recent interest because of their unique genetic adaptations to high altitude. Recent studies have demonstrated that the Tibetan EPAS1 haplotype is involved in high altitude-adaptation and originated in an archaic Denisovan-related population. We sequenced the whole-genomes of 27 Tibetans and conducted analyses to infer a detailed history of demography and natural selection of this population. We detected evidence of population structure between the ancestral Han and Tibetan subpopulations as early as 44 to 58 thousand years ago, but with high rates of gene flow until approximately 9 thousand years ago. The CMS test ranked EPAS1 and EGLN1 as the top two positive selection candidates, and in addition identified PTGIS, VDR, and KCTD12 as new candidate genes. The advantageous Tibetan EPAS1 haplotype shared many variants with the Denisovan genome, with an ancient gene tree divergence between the Tibetan and Denisovan haplotypes of about 1 million years ago. With the exception of EPAS1, we observed no evidence of positive selection on Denisovan-like haplotypes.

Birds and other vertebrates display stunning variation in pigmentation patterning, yet the genes controlling this diversity remain largely unknown. Rock pigeons (Columba livia) are fundamentally one of four color pattern phenotypes, in decreasing order of melanism: T-check, checker, bar (ancestral), or barless. Using whole-genome scans, we identified NDP as a candidate gene for this variation. Allele-specific expression differences in NDP indicate cis-regulatory divergence between ancestral and melanistic alleles. Sequence comparisons suggest that derived alleles originated in the speckled pigeon (Columba guinea), providing a striking example of introgression. In contrast, barless rock pigeons have an increased incidence of vision defects and, like human families with hereditary blindness, carry start-codon mutations in NDP. In summary, we find that both coding and regulatory variation in the same gene drives wing pattern diversity, and post-domestication introgression supplied potentially advantageous melanistic alleles to feral populations of this ubiquitous urban bird.

Extensive DNA sequence data have made it possible to reconstruct human evolutionary history in unprecedented detail. We introduce a method to study the past several hundred thousand years. Our results show that (i) the Neanderthal-Denisovan lineage declined to a small size just after separating from the modern lineage, (ii) Neanderthals and Denisovans separated soon thereafter, and (iii) the subsequent Neanderthal population was large and deeply subdivided. They also (iv) support previous estimates of gene flow from Neanderthals into modern Eurasians. These results suggest an archaic human diaspora early in the Middle Pleistocene.human evolution | archaic admixture | introgression | Neanderthals | Denisovans A round 600 kya, Europe was invaded by large-brained hominins using Acheulean stone tools (1, 2). They were probably African immigrants, because similar fossils and tools occur earlier in Africa. They have been called archaic Homo sapiens, Homo heidelbergensis, and early Neanderthals, yet they remain mysterious. They may have been ancestors of Neanderthals and modern humans (3), or ancestors of Neanderthals only (4, 5), or an evolutionary dead end. According to this last hypothesis, they were replaced later in the Middle Pleistocene by a wave of African immigrants that separated Neanderthals from modern humans and introduced the Levallois stone tool tradition to Europe (6, 7). To address this controversy, we introduce a statistical method and use it to study genetic data of Africans, Eurasians, Neanderthals, and Denisovans.Our method extends an idea introduced by Reich et al. (8,9). Their "ABBA-BABA" statistics infer admixture from the frequency with which derived alleles are shared by pairs of samples. As we have shown (10), these estimators have large biases when populations receive gene flow from more than one source. The magnitudes of these biases depend on the sizes and separation times of ancestral populations. Our method avoids bias by estimating these parameters simultaneously.To accomplish this, our method uses an expanded dataset. ABBA-BABA statistics summarize allele sharing by pairs of samples. We extend this approach to include larger subsets, such as trios of samples, and to use all available subsets. This opens a rich and heretofore unused window into population history. Nucleotide Site PatternsAlthough our method can accommodate complex models, we work here with a four-population model of history (Fig. 1A), which has broad empirical support (11,12). In this model, Neanderthals (N ) contribute genes to Eurasians (Y ) but not to Africans (X ). The model allows no gene flow from Denisovans (D), for reasons explained below. Combinations of uppercase letters, such as ND, refer to the population ancestral to N and D. Lowercase letters, such as n and d , refer to individual haploid genomes sampled from these populations.The gene tree describes how genes coalesce within the tree of populations. Fig. 1B illustrates one of many possible gene trees. Although closely linked nucleotide sites tend to share...

This article evaluates bias in one class of methods used to estimate archaic admixture in modern humans. These methods study the pattern of allele sharing among modern and archaic genomes. They are sensitive to "ghost" admixture, which occurs when a population receives archaic DNA from sources not acknowledged by the statistical model. The effect of ghost admixture depends on two factors: branch-length bias and population-size bias. Branch-length bias occurs because a given amount of admixture has a larger effect if the two populations have been separated for a long time. Population-size bias occurs because differences in population size distort branch lengths in the gene genealogy. In the absence of ghost admixture, these effects are small. They become important, however, in the presence of ghost admixture. Estimators differ in the pattern of response. Increasing a given parameter may inflate one estimator but deflate another. For this reason, comparisons among estimators are informative. Using such comparisons, this article supports previous findings that the archaic population was small and that Europeans received little gene flow from archaic populations other than Neanderthals. It also identifies an inconsistency in estimates of archaic admixture into Melanesia.

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