ng.303 - Accelerated genetic drift on chromosome X during...

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Unformatted text preview: Accelerated genetic drift on chromosome X during the human dispersal out of Africa Alon Keinan 1,2 , James C Mullikin 3 , Nick Patterson 2 & David Reich 1,2 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. In a population with equal numbers of females and males, there are three copies of chromosome X for every four autosomes. As a consequence, in a population of constant size in the absence of natural selection, the average time since the most recent common genetic ancestor (tMRCA) of two unrelated individuals should be 3/4 on chromosome X of what it is on the autosomes, and allele frequency change on the autosomes should occur at 3/4 the rate of chromosome X. Population genetic studies in small datasets have found deviations from these expectations. For example, one study 1 found that the ratio of chromosome X–to-autosome diversity in non-African human populations was less than 3/4, whereas a later study observed an increased ratio in both African and non-African populations 2 . Geno- mic-scale human-variation datasets offer the possibility of more precise estimates 3,4 , and have generally found more allele frequency differen- tiation on chromosome X between populations 3–6 . However, these observations have been difficult to interpret in terms of history or selection because the frequency distributions on chromosome X and the autosomes were biased by the different ways in which SNPs were selected from these two parts of the genome (‘ascertainment bias’) 3,7,8 . We compared patterns of variation on chromosome X and the autosomes using two uniformly collected, genome-scale datasets that we had originally assembled for the autosomes 8 and that we now extend to chromosome X. Both datasets are several orders of magni- tude larger than previous datasets that have been available for compar- ing these two parts of the genome, allowing qualitatively new insights into history. The first dataset consists of about 130,000 SNPs that were discovered as differences between two chromosomes of samples of either West African, North European or East Asian ancestry, and then genotyped in more samples of all three ancestries...
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This note was uploaded on 03/20/2010 for the course BIOCHEM 410 taught by Professor Whien during the Winter '10 term at Ohio State.

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ng.303 - Accelerated genetic drift on chromosome X during...

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