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Mol Biol Evol. 2014 Sep;31(9):2267-82. doi: 10.1093/molbev/msu166. Epub 2014 May 15.

Evidence for increased levels of positive and negative selection on the X chromosome versus autosomes in humans.

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Arizona Research Laboratories Division of Biotechnology, University of ArizonaDepartment of Ecology and Evolution, Stony Brook University.
Department of Molecular and Cellular Biology, University of Arizona.
Arizona Research Laboratories Division of Biotechnology, University of Arizona.
Department of Mathematics, University of Arizona.
Arizona Research Laboratories Division of Biotechnology, University of Arizona


Partially recessive variants under positive selection are expected to go to fixation more quickly on the X chromosome as a result of hemizygosity, an effect known as faster-X. Conversely, purifying selection is expected to reduce substitution rates more effectively on the X chromosome. Previous work in humans contrasted divergence on the autosomes and X chromosome, with results tending to support the faster-X effect. However, no study has yet incorporated both divergence and polymorphism to quantify the effects of both purifying and positive selection, which are opposing forces with respect to divergence. In this study, we develop a framework that integrates previously developed theory addressing differential rates of X and autosomal evolution with methods that jointly estimate the level of purifying and positive selection via modeling of the distribution of fitness effects (DFE). We then utilize this framework to estimate the proportion of nonsynonymous substitutions fixed by positive selection (α) using exome sequence data from a West African population. We find that varying the female to male breeding ratio (β) has minimal impact on the DFE for the X chromosome, especially when compared with the effect of varying the dominance coefficient of deleterious alleles (h). Estimates of α range from 46% to 51% and from 4% to 24% for the X chromosome and autosomes, respectively. While dependent on h, the magnitude of the difference between α values estimated for these two systems is highly statistically significant over a range of biologically realistic parameter values, suggesting faster-X has been operating in humans.


X chromosome; autosomes; distribution of fitness effects; humans; positive selection; purifying selection

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