Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.
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Demographic history of Ryukyu islanders at the southern part of the Japanese Archipelago inferred from whole-genome resequencing data
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European Nucleotide Archive
Raw data for 279 genomes for which the informed consent documentation is consistent with fully public data release are available through the EBI European Nucleotide Archive under accession numbers PRJEB9586 and ERP010710. For the remaining 21 genomes (designated by code ‘Y’ in the seventh column of Supplementary Data Table 1), data are deposited at the European Genome-phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001001959. Data for these 21 genomes can be obtained by submitting to the EGA Data Access Committee a signed letter containing the following text: “(a) I will not distribute the data outside my collaboration; (b) I will not post the data publicly; (c) I will make no attempt to connect the genetic data to personal identifiers for the samples; and (d) I will not use the data for any commercial purposes.” Compact versions of the SGDP dataset and software for accessing it are available at (http://genetics.med.harvard.edu/reichlab/Reich_Lab/Datasets.html). The short tandem repeat (STR) genotypes are available through dbVar under accession number nstd128 (http://www.ncbi.nlm.nih.gov/dbvar).
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We thank the volunteers who donated samples. We thank H. Blanche, N. Boivin, H. Cann (deceased), E. Eichler, H. Greely, M. Petraglia, K. Prüfer, A. Rogers, M. Steinrücken, U. Stenzel and P. Sudmant for comments, critiques, discussions, or advice on assembling samples. We thank S. Fan for uploading 21 genomes to the European Genome-phenome archive. The sequencing was funded by the Simons Foundation (SFARI 280376) and the US National Science Foundation (BCS-1032255). I.M. was supported by a Long Term Fellowship grant LT001095/2014 from the Human Frontier Science program. P.S. was supported by the Wenner-Gren foundation and the Swedish Research Council (VR grant 2014-453). T.W. and M.G. were supported by an NIJ grant 2014-DN-BX-K089. Y.E. was supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund and by NIJ grant 2014-DN-BX-K089. D.L. was supported by the Natural Sciences and Engineering Research Council of Canada. T.K. was supported by ERC Starting Investigator grant FP7 - 261213. R.S. received support from Russian Foundation for Basic Research (#15-04-02543). S.D. received support from the Russian Foundation for Basic Research (#16-34-00599). R.K., E.K. and S.L. were supported by the Russian Foundation for Basic Research (11-04-00725-a). E.B. was supported by the Russian Foundation for Basic Research (16-06-00303). O.B. was supported by the Russian Scientific Fund (14-04-00827) and by the Russian Foundation for Basic Research (16-04-00890). D.M.B., H.S., E.M., R.V. and M.M. were supported by Institutional Research Funding from the Estonian Research Council IUT24-1 and by the European Regional Development Fund (European Union) through the Centre of Excellence in Genomics to Estonian Biocentre and University of Tartu. D.C. was supported by the Spanish MINECO grant CGL-44351-P. L.B.J. and W.S.W. were supported by NIH grant GM59290. S.A.T. was supported by NIH grants 5DP1ES022577 05, 1R01DK104339-01, and 1R01GM113657-01. C.T.-S. and Y.X. were supported by The Wellcome Trust grant 098051. C.M.B. was supported by NSF grants 0924726 and 1153911. K.T. was supported by CSIR Network Project grant (GENESIS: BSC0121). J.P.S. and Y.S.S. were supported in part by an NIH grant R01-GM094402, and a Packard Fellowship for Science and Engineering. G.R., J.K and S.P. were funded by the Max Planck Society. N.P. and D.R. were supported by NIH grant GM100233 and D.R. is a Howard Hughes Medical Institute investigator.
U.H. is employed by NextBio, a division of Illumina Ltd.
Reviewer Information Nature thanks P. Bellwood and S. Ramachandran and the other anonymous reviewer(s) for their contribution to the peer review of this work.
Extended data figures and tables
Extended Data Figure 1 Heat map of fraction of heterozygous sites missed in the 1000 Genomes project.
For each sample, we examine all heterozygous sites passing filter level 1, and compute the fraction included as known polymorphisms in the 1000 Genomes project.
a, Mean STR length is reported as the average of the length difference (in base pairs) from the GRCh37 reference for each genotype. Bubble area scales with the number of calls compared at each point. b, c, The first two principal components after performing principal component analysis on tetranucleotide and homopolymer genotypes, respectively. Colours represent the region of origin of each sample. d, Pairwise FST values between populations computed using only SNPs versus using combined SNP + STR loci. e, Block jackknife standard errors for the SNP versus SNP + STR FST analysis. The red dashed lines give the best-fit line, described by the formula in red. The black dashed line denotes the diagonal.
We carried out unsupervised ADMIXTURE 1.238,43 analysis over the 300 SGDP individuals in 20 replicates with randomly chosen initial seeds, varying the number of ancestral populations between K = 2 and K = 12 and using default fivefold cross-validation (–cv flag). We used genotypes of at least filter level 1, and restricted analysis to sites where at least two individuals carried the variant allele (as singleton variants are non-informative for population clustering). After further filtering of sites with at least 99% completeness and performing linkage-disequilibrium-based pruning in PLINK 1.944,45 with parameters (–indep-pairwise 1000 100 0.2), a total of 482,515 single nucleotide polymorphisms remained. This figure shows the highest likelihood replicate for each value of K. We found that log likelihood monotonically increases with K, while the value K = 5 minimizes cross-validation error (not shown). The solution at K = 5 corresponds to major continental groups (Sub-Saharan Africans, Oceanians, East Asians, Native Americans, and West Eurasians), but we show the full range of K here as they illustrate finer-scale population structure that may be useful to users of the data.
a, Principal component analysis. b, Neighbour-joining tree based on FST values for all populations with at least two samples.
Extended Data Figure 5 Fewer accumulated mutations in Africans than in non-Africans confirmed by mapping to chimpanzee.
We compute a statistic D (Population A, Population B, Chimp), measuring the difference in the rate of matching to chimpanzee in Population A compared to Population B. The evidence of mismatching to chimpanzee is seen when we restrict to the male X chromosome to eliminate possible effects due to differences in heterozygosity across populations, and map to the chimpanzee genome which is phylogenetically symmetrically related to all present-day humans. We find that in 78 randomly chosen Population A = African and Population B = non-African pairs of males, transversion substitutions show no consistent skew from zero, but transition substitutions do.
The red line denotes the 99.9% quantile cut-off. The genes in the top five regions are labelled. a, Scan for selection on the San terminal branch. b, Scan for selection on the non-San terminal branch. c, Scan for selection on the ancestral modern human branch.
Extended Data Figure 7 Scan for genomic locations where the great majority of present-day humans share a recent common ancestor.
We carried out PSMC analysis on 40 pairs of haploid genomes chosen to sample some of the most deeply divergent present-day human lineages. We recorded the time since the most recent common ancestor (TMRCA) at each position, and rescaled to obtain an estimate of absolute time (Supplementary Information section 12). a, Distribution across the genome of the fraction of TMRCAs below specified date cut-offs. For the 100 kya cut-off, the maximum fraction observed anywhere in the genome is 68%. b, Distribution across the genome of the date T at which specified fractions of sample pairs are inferred to have a TMRCA less than T. c, Percentile points of the cumulative distribution function of B.
This file contains Supplementary Text and Data, Supplementary Tables Supplementary Figures and additional references (see Contents for details). (PDF 8661 kb)
This file shows the data by each sample studied. (XLSX 124 kb)
This table shows the top hits for 3P-CLR run. (XLSX 71 kb)
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Mallick, S., Li, H., Lipson, M. et al. The Simons Genome Diversity Project: 300 genomes from 142 diverse populations. Nature 538, 201–206 (2016). https://doi.org/10.1038/nature18964
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