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."A DMIXTURE between populations is a fundamental process that shapes genetic variation and disease risk. For example, African Americans and Latinos derive their genomes from mixtures of individuals who trace their ancestry to divergent populations. Study of the ancestral origin of the admixed individuals provides an opportunity to infer the history of the ancestral groups, some of whom may no longer be extant. The two main classes of methods in this field are local ancestry-based methods and global ancestry-based methods. Local ancestry-based methods such as LAMP (Sankararaman et al. 2008), HAPMIX (Price et al. 2009), and PCADMIX (Brisbin 2010) deconvolve ancestry at each locus in the genome and provide individual-level information about ancestry. While these methods provide valuable insights into the recent history of populations, they have reduced power to detect older events. The most commonly used methods for studying global ancestry are principal component analysis (PCA) (Patterson et al. 2006) and model-based clustering methods such as STRUCTURE (Pritchard et al. 2000) and ADMIXTURE (Alexander et al. 2009). While these are powerful tools for detecting population substructure, they do not provide any formal tests for admixture (the patterns in data detected using these methods can be generated by multiple population histories). For instance, Novembre et al. (2008) showed that isolation-by-distance can generate PCA gradients that are similar to those that arise from long-distance historical migrations, making PCA results difficult to interpret from a historical perspective. STRUCTURE/ADMIXTURE results are also difficult to interpret historically, because these methods work either without explicitly fitting a historical model or by fitting a model that assumes that all the populations have radiated from a single ancestral group, which is unr...

We present a high-quality genome sequence of a Neandertal woman from Siberia. We show that her parents were related at the level of half siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neandertal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neandertals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high quality Neandertal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neandertals and Denisovans.

We present a DNA library preparation method that has allowed us to reconstruct a high coverage (30X) 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.