Weak selection revealed by the whole-genome comparison of the X chromosome and autosomes of human and chimpanzee

Abstract

The effect of weak selection driving genome evolution has attracted much attention in the last decade, but the task of measuring the strength of such selection is particularly difficult. A useful approach is to contrast the evolution of X-linked and autosomal genes in two closely related species in a whole-genome analysis. If the fitness effect of mutations is recessive, X-linked genes should evolve more rapidly than autosomal genes when the mutations are advantageous, and they should evolve more slowly than autosomal genes when the mutations are deleterious. We found synonymous substitutions on the X chromosome of human and chimpanzee to be less frequent than those on the autosomes. When calibrated against substitutions in the intergenic regions and pseudogenes to filter out the differences in the mutation rate and ancestral population size between X chromosomes and autosomes, X-linked synonymous substitutions are still 10% less frequent. At least 90% of the synonymous substitutions in human and chimpanzee are estimated to be deleterious, but the fitness effect is weaker than the effect of genetic drift. However, X-linked nonsynonymous substitutions are approximately 30% more frequent than autosomal ones, suggesting the fixation of advantageous mutations that are recessive.

Fig. 1.

The fixation probabilities for X-linked and autosomal mutations under selection, relative to the neutral ones. The fixation probabilities are functions of effective population size (N_e), selective coefficient (s), dominance coefficient (h), and the effective male-to-female ratio (m). (See Supporting Methods.) Data shown are for cases of N_e = 10,000, h = 0.1, and m = 0.33.

Fig. 2.

Estimation of p (the proportion of synonymous substitutions under negative selection) and 2N_es when the X/A ratio is 0.9 (see the last two rows of Table 1). For all values of 2N_es, p is always >0.85. The K_s/K_i value is also a function of 2N_es; the case for h = 0.1, m = 0.33, and N_e = 10,000 is shown in the lower curve. The observed autosomal K_s/K_i at 0.791 further constrains 2N_es to <1 and p to >0.9. K_i is assumed to be the neutral rate.