Accelerated genetic drift on chromosome X during the human dispersal out of Africa

Article metrics


Comparisons of chromosome X and the autosomes can illuminate differences in the histories of males and females as well as shed light on the forces of natural selection. We compared the patterns of variation in these parts of the genome using two datasets that we assembled for this study that are both genomic in scale. Three independent analyses show that around the time of the dispersal of modern humans out of Africa, chromosome X experienced much more genetic drift than is expected from the pattern on the autosomes. This is not predicted by known episodes of demographic history, and we found no similar patterns associated with the dispersals into East Asia and Europe. We conclude that a sex-biased process that reduced the female effective population size, or an episode of natural selection unusually affecting chromosome X, was associated with the founding of non-African populations.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: The distribution of allele frequencies on chromosome X does not match the expectation from the autosomes in non-African populations.
Figure 2: Gene-centric natural selection, or natural selection localized to specific regions of chromosome X, fail to explain the signal of accelerated genetic drift.


  1. 1

    Hammer, M.F. et al. Heterogeneous patterns of variation among multiple human x–linked loci: the possible role of diversity-reducing selection in non-Africans. Genetics 167, 1841–1853 (2004).

  2. 2

    Hammer, M.F., Mendez, F.L., Cox, M.P., Woerner, A.E. & Wall, J.D. Sex-biased evolutionary forces shape genomic patterns of human diversity. PLoS Genet. 4, e1000202 (2008).

  3. 3

    The International HapMap Consortium. A second generation human haplotype map of over 3.1 million SNPs. Nature 449, 851–861 (2007).

  4. 4

    Li, J.Z. et al. Worldwide human relationships inferred from genome-wide patterns of variation. Science 319, 1100–1104 (2008).

  5. 5

    Akey, J.M., Zhang, G., Zhang, K., Jin, L. & Shriver, M.D. Interrogating a high-density SNP map for signatures of natural selection. Genome Res. 12, 1805–1814 (2002).

  6. 6

    Voight, B.F., Kudaravalli, S., Wen, X. & Pritchard, J.K. A map of recent positive selection in the human genome. PLoS Biol. 4, e72 (2006).

  7. 7

    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).

  8. 8

    Keinan, A., Mullikin, J.C., Patterson, N. & Reich, D. Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans. Nat. Genet. 39, 1251–1255 (2007).

  9. 9

    Fay, J.C. & Wu, C.I. A human population bottleneck can account for the discordance between patterns of mitochondrial versus nuclear DNA variation. Mol. Biol. Evol. 16, 1003–1005 (1999).

  10. 10

    Garrigan, D. & Hammer, M.F. Reconstructing human origins in the genomic era. Nat. Rev. Genet. 7, 669–680 (2006).

  11. 11

    Pool, J.E. & Nielsen, R. Population size changes reshape genomic patterns of diversity. Evolution Int. J. Org. Evolution 61, 3001–3006 (2007).

  12. 12

    Andolfatto, P. Contrasting patterns of X-linked and autosomal nucleotide variation in Drosophila melanogaster and Drosophila simulans. Mol. Biol. Evol. 18, 279–290 (2001).

  13. 13

    Betancourt, A.J., Kim, Y. & Orr, H.A. A pseudohitchhiking model of X vs. autosomal diversity. Genetics 168, 2261–2269 (2004).

  14. 14

    Wall, J.D., Andolfatto, P. & Przeworski, M. Testing models of selection and demography in Drosophila simulans. Genetics 162, 203–216 (2002).

  15. 15

    Charlesworth, B., Coyne, J.A. & Barton, N.H. The relative rates of evolution of sex chromosomes and autosomes. Am. Nat. 130, 113–146 (1987).

  16. 16

    Charlesworth, B., Morgan, M.T. & Charlesworth, D. The effect of deleterious mutations on neutral molecular variation. Genetics 134, 1289–1303 (1993).

  17. 17

    Haddrill, P.R., Thornton, K.R., Charlesworth, B. & Andolfatto, P. Multilocus patterns of nucleotide variability and the demographic and selection history of Drosophila melanogaster populations. Genome Res. 15, 790–799 (2005).

  18. 18

    Storz, J.F., Payseur, B.A. & Nachman, M.W. Genome scans of DNA variability in humans reveal evidence for selective sweeps outside of Africa. Mol. Biol. Evol. 21, 1800–1811 (2004).

  19. 19

    Kayser, M. et al. Reduced Y-chromosome, but not mitochondrial DNA, diversity in human populations from West New Guinea. Am. J. Hum. Genet. 72, 281–302 (2003).

  20. 20

    Seielstad, M.T., Minch, E. & Cavalli-Sforza, L.L. Genetic evidence for a higher female migration rate in humans. Nat. Genet. 20, 278–280 (1998).

  21. 21

    Marlowe, F.W. Hunter-gatherers and human evolution. Evol. Anthropol. 14, 54–67 (2005).

  22. 22

    Bedoya, G. et al. Admixture dynamics in Hispanics: a shift in the nuclear genetic ancestry of a South American population isolate. Proc. Natl. Acad. Sci. USA 103, 7234–7239 (2006).

  23. 23

    Hammer, M.F. et al. Hierarchical patterns of global human Y-chromosome diversity. Mol. Biol. Evol. 18, 1189–1203 (2001).

  24. 24

    Helgason, A. et al. Estimating Scandinavian and Gaelic ancestry in the male settlers of Iceland. Am. J. Hum. Genet. 67, 697–717 (2000).

  25. 25

    Parra, E.J. et al. Estimating African American admixture proportions by use of population-specific alleles. Am. J. Hum. Genet. 63, 1839–1851 (1998).

  26. 26

    Caballero, A. On the effective size of populations with separate sexes, with particular reference to sex-linked genes. Genetics 139, 1007–1011 (1995).

  27. 27

    Charlesworth, B. The effect of life-history and mode of inheritance on neutral genetic variability. Genet. Res. 77, 153–166 (2001).

  28. 28

    Patterson, N. et al. Methods for high-density admixture mapping of disease genes. Am. J. Hum. Genet. 74, 979–1000 (2004).

  29. 29

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

  30. 30

    Tang, K. et al. Chip-based genotyping by mass spectrometry. Proc. Natl. Acad. Sci. USA 96, 10016–10020 (1999).

Download references


We thank C. Aquadro, O. Bar-Yosef, M. Bernstein, B. Charlesworth, A. Helgason, E. Lander, D. Lieberman, K. Lohmueller, S. Myers, S. Pääbo, A. Price, S. Schaffner and C. Stringer for comments, and J. Neubauer and A. Waliszewska for genotyping SNPs discovered in two West African X chromosomes. The orangutan sequence reads were generated by the Washington University genome sequencing center (; we thank R. Wilson for permission to use these data. J.C.M. was supported by the Intramural Research Program of the US National Human Genome Research Institutes (NHGRI), N.P. by a K-01 career transition award from the US National Institutes of Health (NIH) and D.R. by a Burroughs Wellcome Career Development Award in the Biomedical Sciences. A.K., N.P. and D.R. were also supported by NIH grant U01 HG004168.

Author information

A.K. and D.R. designed the study; J.C.M. and A.K. assembled datasets; D.R., A.K. and J.C.M. conducted genotyping; A.K., J.C.M. and D.R. performed analyses; N.P. provided guidance on statistical analyses; A.K. and D.R. interpreted results and wrote the manuscript, which was edited by all co-authors.

Correspondence to Alon Keinan or David Reich.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 1–4, Supplementary Figures 1 and 2, Supplementary Methods and Supplementary Note (PDF 530 kb)

Rights and permissions

Reprints and Permissions

About this article

Further reading