The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

Europe has played a major role in dog evolution, harbouring the oldest uncontested Palaeolithic remains and having been the centre of modern dog breed creation. Here we sequence the genomes of an Early and End Neolithic dog from Germany, including a sample associated with an early European farming community. Both dogs demonstrate continuity with each other and predominantly share ancestry with modern European dogs, contradicting a previously suggested Late Neolithic population replacement. We find no genetic evidence to support the recent hypothesis proposing dual origins of dog domestication. By calibrating the mutation rate using our oldest dog, we narrow the timing of dog domestication to 20,000–40,000 years ago. Interestingly, we do not observe the extreme copy number expansion of the AMY2B gene characteristic of modern dogs that has previously been proposed as an adaptation to a starch-rich diet driven by the widespread adoption of agriculture in the Neolithic.

Despite strides in characterizing human history from genetic polymorphism data, progress in identifying genetic signatures of recent demography has been limited. Here we identify very recent fine-scale population structure in North America from a network of over 500 million genetic (identity-by-descent, IBD) connections among 770,000 genotyped individuals of US origin. We detect densely connected clusters within the network and annotate these clusters using a database of over 20 million genealogical records. Recent population patterns captured by IBD clustering include immigrants such as Scandinavians and French Canadians; groups with continental admixture such as Puerto Ricans; settlers such as the Amish and Appalachians who experienced geographic or cultural isolation; and broad historical trends, including reduced north-south gene flow. Our results yield a detailed historical portrait of North America after European settlement and support substantial genetic heterogeneity in the United States beyond that uncovered by previous studies.

Europe has played a major role in dog evolution, harbouring the oldest uncontested Paleolithic remains and having been the centre of modern dog breed creation. We sequenced the whole genomes of an Early and End Neolithic dog from Germany, including a sample associated with one of Europe’s earliest farming communities. Both dogs demonstrate continuity with each other and predominantly share ancestry with modern European dogs, contradicting a previously suggested Late Neolithic population replacement. Furthermore, we find no genetic evidence to support the recent hypothesis proposing dual origins of dog domestication. By calibrating the mutation rate using our oldest dog, we narrow the timing of dog domestication to 20,000-40,000 years ago. Interestingly, we do not observe the extreme copy number expansion of the AMY2B gene that is characteristic of modern dogs and has previously been proposed as an adaptation to a starch-rich diet driven by the widespread adoption of agriculture in the Neolithic.

Phased haplotype sequences are a key component in many population genetic analyses since variation in haplotypes reflects the action of recombination, selection, and changes in population size. In humans, haplotypes are typically estimated from unphased sequence or genotyping data using statistical models applied to large reference panels. To assess the importance of correct haplotype phase on population history inference, we performed fosmid pool sequencing and resolved phased haplotypes of five individuals from diverse African populations (including Yoruba, Esan, Gambia, Maasai, and Mende). We physically phased 98% of heterozygous SNPs into haplotype-resolved blocks, obtaining a block N50 of 1 Mbp. We combined these data with additional phased genomes from San, Mbuti, Gujarati, and Centre de'Etude du Polymorphism Humain European populations and analyzed population size and separation history using the pairwise sequentially Markovian coalescent and multiple sequentially Markovian coalescent models. We find that statistically phased haplotypes yield a more recent split-time estimation compared with experimentally phased haplotypes. To better interpret patterns of cross-population coalescence, we implemented an approximate Bayesian computation approach to estimate population split times and migration rates by fitting the distribution of coalescent times inferred between two haplotypes, one from each population, to a standard isolation-with-migration model. We inferred that the separation between hunter-gatherer populations and other populations happened 120-140 KYA, with gene flow continuing until 30-40 KYA; separation between west-African and out-ofAfrican populations happened 70-80 KYA; while the separation between Maasai and out-of-African populations happened 50 KYA.KEYWORDS fosmid pool sequencing; haplotype; population split time; PSMC; MSMC; approximate Bayesian computation H APLOTYPES contain rich information about population history and are shaped by population size, natural selection, and recombination (Veeramah and Hammer 2014;Schraiber and Akey 2015). Due to historic recombination events there are 100s of 1000s of pairs of loci along a chromosome that have distinct histories. Recent methodological advances permit the estimation of a detailed population demographic history from a single or several whole-genome sequences based on the distribution of coalescent times across the genome. For example, Li and Durbin (2011) developed the pairwise sequentially Markovian coalescent (PSMC) model to reconstruct the distribution of the time since the most recent common ancestor (TMRCA) between the two alleles of an individual, and infer population size changes over time. Typically, these TMRCA values are calculated using the two haploid genomes that compose the diploid genome of a single sample (Li and Durbin 2011). When PSMC is applied to two haplotypes obtained from different populations, the inferred TMRCA distribution is informative about the timing of population splits, since the time after which near...