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

Krishna R. Veeramah, Ryan N. Gutenkunst, August E. Woerner, Joseph C. Watkins, Michael F. Hammer

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Partially recessive variants under positive selection are expected to go to fixationmore 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 polymorphismto 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 (a) using exome sequence data from aWest African population. We find that varying the female to male breeding ratio (b) 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 a 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 a 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.

Original languageEnglish (US)
Pages (from-to)2267-2282
Number of pages16
JournalMolecular biology and evolution
Issue number9
StatePublished - Sep 2014


  • Autosomes
  • Distribution of fitness effects
  • Humans
  • Positive selection
  • Purifying selection
  • X chromosome

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


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