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Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans

Nature Genetics volume 39, pages 1251–1255 (2007)Cite this article

Abstract

Large data sets on human genetic variation have been collected recently, but their usefulness for learning about history and natural selection has been limited by biases in the ways polymorphisms were chosen. We report large subsets of SNPs from the International HapMap Project1,2 that allow us to overcome these biases and to provide accurate measurement of a quantity of crucial importance for understanding genetic variation: the allele frequency spectrum. Our analysis shows that East Asian and northern European ancestors shared the same population bottleneck expanding out of Africa but that both also experienced more recent genetic drift, which was greater in East Asians.

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Figure 1: Discovery of SNPs by comparing two sequencing reads from an individual of known ancestry.
Figure 2: Derived allele frequency spectra in each population.
Figure 3: Modeling provides an excellent fit to the observed allele frequency spectra.

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References

  1. The International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).

  2. The International HapMap Consortium. The Phase II HapMap. (in the press).

  3. Adams, A.M. & Hudson, R.R. Maximum-likelihood estimation of demographic parameters using the frequency spectrum of unlinked single-nucleotide polymorphisms. Genetics 168, 1699–1712 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Marth, G.T., Czabarka, E., Murvai, J. & Sherry, S.T. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pluzhnikov, A., Di Rienzo, A. & Hudson, R.R. Inferences about human demography based on multilocus analyses of noncoding sequences. Genetics 161, 1209–1218 (2002).

    PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Voight, B.F. et al. Interrogating multiple aspects of variation in a full resequencing data set to infer human population size changes. Proc. Natl. Acad. Sci. USA 102, 18508–18513 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. Clark, A.G., Hubisz, M.J., Bustamante, C.D., Williamson, S.H. & Nielsen, R. Ascertainment bias in studies of human genome-wide polymorphism. Genome Res. 15, 1496–1502 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nielsen, R., Hubisz, M.J. & Clark, A.G. Reconstituting the frequency spectrum of ascertained single-nucleotide polymorphism data. Genetics 168, 2373–2382 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hinds, D.A. et al. Whole-genome patterns of common DNA variation in three human populations. Science 307, 1072–1079 (2005).

    Article  CAS  PubMed  Google Scholar 

  11. Garrigan, D., Mobasher, Z., Kingan, S.B., Wilder, J.A. & Hammer, M.F. Deep haplotype divergence and long-range linkage disequilibrium at xp21.1 provide evidence that humans descend from a structured ancestral population. Genetics 170, 1849–1856 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Williamson, S.H. et al. Simultaneous inference of selection and population growth from patterns of variation in the human genome. Proc. Natl. Acad. Sci. USA 102, 7882–7887 (2005).

    Article  CAS  PubMed  Google Scholar 

  13. Stephens, M., Sloan, J.S., Robertson, P.D., Scheet, P. & Nickerson, D.A. Automating sequence-based detection and genotyping of SNPs from diploid samples. Nat. Genet. 38, 375–381 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Prugnolle, F., Manica, A. & Balloux, F. Geography predicts neutral genetic diversity of human populations. Curr. Biol. 15, R159–R160 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ramachandran, S. et al. Support from the relationship of genetic and geographic distance in human populations for a serial founder effect originating in Africa. Proc. Natl. Acad. Sci. USA 102, 15942–15947 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Conrad, D.F. et al. A worldwide survey of haplotype variation and linkage disequilibrium in the human genome. Nat. Genet. 38, 1251–1260 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Bowcock, A.M. et al. Drift, admixture, and selection in human evolution: a study with DNA polymorphisms. Proc. Natl. Acad. Sci. USA 88, 839–843 (1991).

    Article  CAS  PubMed  Google Scholar 

  18. Weir, B.S. & Cockerham, C.C. Estimating F-statistics for the analysis of population structure. Evolution Int. J. Org. Evolution 38, 1358–1370 (1984).

    CAS  Google Scholar 

  19. Becquet, C., Patterson, N., Stone, A.C., Przeworski, M. & Reich, D. Genetic structure of chimpanzee populations. PLoS Genet 3, e66 (2007) (doi:10.1371/journal.pgen.0030066).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Hewitt, G. The genetic legacy of the Quaternary ice ages. Nature 405, 907–913 (2000).

    Article  CAS  PubMed  Google Scholar 

  22. Plagnol, V. & Wall, J.D. Possible ancestral structure in human populations. PLoS Genet. 2, e105 (2006) (doi:10.1371/journal.pgen.0020105).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lahr, M.M. & Foley, R. Multiple dispersals and modern human origins. Evol. Anthropol. 3, 48–60 (2005).

    Article  Google Scholar 

  24. Stringer, C.B., Grun, R., Schwarcz, H.P. & Goldberg, P. ESR dates for the hominid burial site of Es Skhul in Israel. Nature 338, 756–758 (1989).

    Article  CAS  PubMed  Google Scholar 

  25. Vanhaereny, M. et al. Middle Paleolithic shell beads in Israel and Algeria. Science 312, 1785–1788 (2006).

    Article  PubMed  Google Scholar 

  26. Ning, Z., Cox, A.J. & Mullikin, J.C. SSAHA: a fast search method for large DNA databases. Genome Res. 11, 1725–1729 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. The Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2005).

  28. Lagarias, J.C., Reeds, J.A., Wright, M.H. & Wright, P.E. Convergence properties of the Nelder-Mead simplex method in low dimensions. SIAM J. Optim. 9, 112–147 (1998).

    Article  Google Scholar 

  29. Lahiri, S.N. Resampling Methods for Dependent Data (Springer, New York, 2003).

    Book  Google Scholar 

  30. Venter, J.C. et al. The sequence of the human genome. Science 291, 1304–1351 (2001).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank D. Altshuler, M. Bernstein, A. Keinan, E. Lander, M. Mandel, M. Mirazon Lahr, A. Price, M. Przeworski, S. Schaffner, C. Stringer and B. Weir for discussions, comments and assistance with stages of this study. We are grateful to G. Marth for sharing the multi-epoch model source code with us. Orangutan sequence traces were produced by the Genome Sequencing Center at Washington University School of Medicine (ftp://ftp.ncbi.nih.gov/pub/TraceDB/pongo_pygmaeus_abelii); we thank R. Wilson for permission to use these data. Sequence traces for the human ABC libraries used in this study were produced by Agencourt Biosciences Corporation and were obtained from ftp://ftp.ncbi.nih.gov/pub/TraceDB/homo_sapiens; we thank D. Smith and E. Eichler for permission to use these data. A.K. was supported by the Rothschild fellowship from Yad Hanadiv foundation. J.C.M. was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health (NIH). N.P. was supported by a career transition award from the NIH. D.R. was supported by NIH grant U01 HG004168 and a Burroughs Wellcome Career Development Award in the Biomedical Sciences.

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Author notes

  1. Alon Keinan and James C Mullikin: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Alon Keinan & David Reich

  2. Broad Institute of Harvard and MIT, Cambridge, 02139, Massachusetts, USA

    Alon Keinan, Nick Patterson & David Reich

  3. Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    James C Mullikin

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  1. Alon Keinan
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Correspondence to Alon Keinan.

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Supplementary Methods, Supplementary Tables 1–5, Supplementary Figures 1 and 2, Supplementary Note (PDF 1007 kb)

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Keinan, A., Mullikin, J., Patterson, N. et al. Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans. Nat Genet 39, 1251–1255 (2007). https://doi.org/10.1038/ng2116

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