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


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.

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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.

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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.

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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.

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Correspondence to Alon Keinan or David Reich.

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

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Keinan, A., Mullikin, J., Patterson, N. et al. Accelerated genetic drift on chromosome X during the human dispersal out of Africa. Nat Genet 41, 66–70 (2009).

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