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Knowledge of genome-wide genealogies for thousands of individuals would simplify most evolutionary analyses for humans and other species, but has remained computationally infeasible. We developed a method, Relate, scaling to > 10,000 sequences while simultaneously estimating branch lengths, mutational ages, and variable historical population sizes, as well as allowing for data errors. Application to 1000 Genomes Project haplotypes produces joint genealogical histories for 26 human populations. Highly diverged lineages are present in all groups, but most frequent in Africa. Outside Africa, these mainly reflect ancient introgression from groups related to Neanderthals and Denisovans, while African signals instead reflect unknown events, unique to that continent. Our approach allows more powerful inferences of natural selection than previously possible. We identify multiple novel regions under strong positive selection, and multi-allelic traits including hair colour, BMI, and blood pressure, showing strong evidence of directional selection, varying among human groups.Large-scale genetic variation datasets are now available for a variety of species, including tens of thousands of humans. In principle, all information about a sample's genetic history is captured by their underlying genealogical history, which records the historical coalescence, recombination, and mutation events that produced the observed variation patterns. In practice, several key existing approaches (e.g., Refs. [1,2]) leverage an underlying coalescent model, because this provides a flexible modelling framework and is the limiting behaviour of a variety of finite-population models 3,4 . However, inference under the coalescent is complicated by the structure of the model, uncertainty over the correct genealogy conditional on observed data, and the large resulting space of possible sample histories 5 . Other approaches 6-11 use more heuristic approximations to the coalescent, sometimes reducing accuracy: regardless, all published existing methods scale to tens or a few hundred samples at most.As a result of these issues, the use of direct genealogy-based inference to detect recombination events, date mutations, and reveal evidence of positive selection has been limited to smaller datasets 1,2 , while for larger datasets approaches based on data summaries 12-14 or downsampling 15,16 have predominated. A diverse set of tools have detected genetic structure that is in good agreement with geopolitical separation over generations 17 .Admixtures of ancient populations have been identified and dated 18 . Other applications have found bottlenecks in population sizes that are consistent with anthropological evidence of initial human migration from the African continent 15,19-21 and evidence of subsequent introgression with archaic humans, such as Neanderthals 22 .We have developed a scalable method, Relate, to estimate genome-wide genealogies (see Figure 1; Methods;URLs for implementation). Relate separates two steps; firstly identifying a genealogical fra...

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived1–8. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.