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Inference of human population history from individual whole-genome sequences

Nature 475, 493–496 (28 July 2011) | Download Citation

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Abstract

The history of human population size is important for understanding human evolution. Various studies1,2,3,4,5 have found evidence for a founder event (bottleneck) in East Asian and European populations, associated with the human dispersal out-of-Africa event around 60 thousand years (kyr) ago. However, these studies have had to assume simplified demographic models with few parameters, and they do not provide a precise date for the start and stop times of the bottleneck. Here, with fewer assumptions on population size changes, we present a more detailed history of human population sizes between approximately ten thousand and a million years ago, using the pairwise sequentially Markovian coalescent model applied to the complete diploid genome sequences of a Chinese male (YH)6, a Korean male (SJK)7, three European individuals (J. C. Venter8, NA12891 and NA12878 (ref. 9)) and two Yoruba males (NA18507 (ref. 10) and NA19239). We infer that European and Chinese populations had very similar population-size histories before 10–20 kyr ago. Both populations experienced a severe bottleneck 10–60 kyr ago, whereas African populations experienced a milder bottleneck from which they recovered earlier. All three populations have an elevated effective population size between 60 and 250 kyr ago, possibly due to population substructure11. We also infer that the differentiation of genetically modern humans may have started as early as 100–120 kyr ago12, but considerable genetic exchanges may still have occurred until 20–40 kyr ago.

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References

  1. 1.

    et al. Linkage disequilibrium in the human genome. Nature 411, 199–204 (2001)

  2. 2.

    , , & The allele frequency spectrum in genome-wide human variation data reveals signals of differential demographic history in three large world populations. Genetics 166, 351–372 (2004)

  3. 3.

    & Possible ancestral structure in human populations. PLoS Genet. 2, e105 (2006)

  4. 4.

    , , & Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans. Nature Genet. 39, 1251–1255 (2007)

  5. 5.

    et al. Statistical evaluation of alternative models of human evolution. Proc. Natl Acad. Sci. USA 104, 17614–17619 (2007)

  6. 6.

    et al. The diploid genome sequence of an Asian individual. Nature 456, 60–65 (2008)

  7. 7.

    et al. The first Korean genome sequence and analysis: full genome sequencing for a socio-ethnic group. Genome Res. 19, 1622–1629 (2009)

  8. 8.

    et al. The diploid genome sequence of an individual human. PLoS Biol. 5, e254 (2007)

  9. 9.

    . A map of human genome variation from population-scale sequencing. Nature 467, 1061–1073 (2010)

  10. 10.

    et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456, 53–59 (2008)

  11. 11.

    et al. The dawn of human matrilineal diversity. Am. J. Hum. Genet. 82, 1130–1140 (2008)

  12. 12.

    Going east: new genetic and archaeological perspectives on the modern human colonization of Eurasia. Science 313, 796–800 (2006)

  13. 13.

    , & mtDNA variation predicts population size in humans and reveals a major Southern Asian chapter in human prehistory. Mol. Biol. Evol. 25, 468–474 (2008)

  14. 14.

    & Approximating the coalescent with recombination. Phil. Trans. R. Soc. B 360, 1387–1393 (2005)

  15. 15.

    & Estimate of the mutation rate per nucleotide in humans. Genetics 156, 297–304 (2000)

  16. 16.

    Why did modern human populations disperse from Africa ca. 60,000 years ago? A new model. Proc. Natl Acad. Sci. USA 103, 9381–9386 (2006)

  17. 17.

    & Archaic admixture in the human genome. Curr. Opin. Genet. Dev. 16, 606–610 (2006)

  18. 18.

    , , & Genomic relationships and speciation times of human, chimpanzee, and gorilla inferred from a coalescent hidden Markov model. PLoS Genet. 3, e7 (2007)

  19. 19.

    , , & Accelerated genetic drift on chromosome X during the human dispersal out of Africa. Nature Genet. 41, 66–70 (2009)

  20. 20.

    et al. A draft sequence of the Neandertal genome. Science 328, 710–722 (2010)

  21. 21.

    et al. Calibrating a coalescent simulation of human genome sequence variation. Genome Res. 15, 1576–1583 (2005)

  22. 22.

    A new radiocarbon revolution and the dispersal of modern humans in Eurasia. Nature 439, 931–935 (2006)

  23. 23.

    Cross-cultural estimation of the human generation interval for use in genetics-based population divergence studies. Am. J. Phys. Anthropol. 128, 415–423 (2005)

  24. 24.

    et al. Haplotype-resolved genome sequencing of a Gujarati Indian individual. Nature Biotechnol. 29, 59–63 (2010)

  25. 25.

    , , & Inferring the joint demographic history of multiple populations from multidimensional SNP frequency data. PLoS Genet. 5, e1000695 (2009)

  26. 26.

    & Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25, 1754–1760 (2009)

  27. 27.

    et al. The sequence alignment/map format and SAMtools. Bioinformatics 25, 2078–2079 (2009)

  28. 28.

    Generating samples under a Wright–Fisher neutral model of genetic variation. Bioinformatics 18, 337–338 (2002)

  29. 29.

    et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010)

  30. 30.

    , , , & Male-driven molecular evolution: a model and nucleotide sequence analysis. Cold Spring Harb. Symp. Quant. Biol. 52, 863–867 (1987)

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Acknowledgements

We are grateful to D. Bentley (Illumina) and J. Wang (Beijing Genomics Institute) for early access to the sequencing data. We thank A. Coghlan for the idea of bootstrapping, and N. Patterson, M. Przeworski, D. Reich, and members of the Durbin research group for discussions and critiques. This work was funded by Wellcome Trust grant WT077192.

Author information

Affiliations

  1. The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK

    • Heng Li
    •  & Richard Durbin

  2. Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA

    • Heng Li

Authors

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Contributions

R.D. proposed the basic strategy and designed the overall study. H.L. developed the theory, implemented the algorithm and analysed results. R.D. and H.L. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Heng Li or Richard Durbin.

The PSMC software package is freely available at http://github.com/lh3/psmc.

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    Supplementary Information

    The file contains Supplementary Text, Supplementary Figures 1-13, Supplementary Tables 1-2 and additional references.

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https://doi.org/10.1038/nature10231

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