Extensive X-linked adaptive evolution in central chimpanzees

Abstract

Surveying genome-wide coding variation within and among species gives unprecedented power to study the genetics of adaptation, in particular the proportion of amino acid substitutions fixed by positive selection. Additionally, contrasting the autosomes and the X chromosome holds information on the dominance of beneficial (adaptive) and deleterious mutations. Here we capture and sequence the complete exomes of 12 chimpanzees and present the largest set of protein-coding polymorphism to date. We report extensive adaptive evolution specifically targeting the X chromosome of chimpanzees with as much as 30% of all amino acid replacements being adaptive. Adaptive evolution is barely detectable on the autosomes except for a few striking cases of recent selective sweeps associated with immunity gene clusters. We also find much stronger purifying selection than observed in humans, and in contrast to humans, we find that purifying selection is stronger on the X chromosome than on the autosomes in chimpanzees. We therefore conclude that most adaptive mutations are recessive. We also document dramatically reduced synonymous diversity in the chimpanzee X chromosome relative to autosomes and stronger purifying selection than for the human X chromosome. If similar processes were operating in the human-chimpanzee ancestor as in central chimpanzees today, our results therefore provide an explanation for the much-discussed reduction in the human-chimpanzee divergence at the X chromosome.Pan troglodytes troglodytes | SNP | site frequency spectrum | distribution of fitness effects | faster X Q uantifying the relative importance of purifying, neutral, and positive selection in shaping divergence between species remains a challenge in evolutionary biology. Beneficial mutations are central for understanding evolution by natural selection. However, the rarity of beneficial mutations has frustrated attempts to characterize their most basic genetic properties in higher organisms (1). One way forward is to combine genome-wide surveys of polymorphism within species and between species divergence to estimate the fraction, α, of mutations that have been fixed by positive selection. Empirical studies, particularly in the Drosophila genus show that mutations fixed by positive selection can make up a sizable fraction (>50%) of the divergence between species in gene coding regions (2) but whether these results are general for mammals, for example, remains unclear. Furthermore we still know very little about the distribution of fitness effects (DFE) of these mutations and even less about their dominance in diploid organisms. Theory predicts and recent empirical studies emphasize that the demographic history as well as variation in mutation and recombination rates can blur footprints of molecular adaptation by Darwinian selection (3, 4). This in turn can complicate the inference of DFE and α (5, 6).In that context, contrasting the DFE and rates of adaptation in autosomes versus sex chromosomes is an elegant strategy to infer the genetic properties...

Weak Selection and Protein Evolution

“…In comparisons limited to a small number of genes, Satta (2001) found higher p N /p S in humans than in chimps; this difference has been confirmed in genome-scale analyses (Hvilsom et al 2012). p N /p S is also higher in humans (0.35) than in mice (0.19; Halligan et al 2010) and rabbits (0.05; Carneiro et al 2012), which is consistent with substantial differences in f9 n .…”

Extreme selective sweeps independently targeted the X chromosomes of the great apes

“…Using McDonald-Kreitman-type analyses, we have previously reported that, in the Central chimpanzee lineage, 30-40% of amino acid changes on the X chromosomes are estimated to have been fixed by positive selection, whereas the autosomes do not show significant signs of positive selection (9). A similar conclusion was recently reached for the human X chromosome (10).…”

Finding the Factors of Reduced Genetic Diversity on X Chromosomes of Macaca fascicularis: Male-Driven Evolution, Demography, and Natural Selection

“…In nonhuman primates, however, some studies have reported much lower ratios. For example, a recent genome-wide resequencing study in central chimpanzees (Pan troglodytes) found a ratio of near 0.5 (Hvilsom et al 2012). A similar ratio was observed in Chinese and Indian rhesus macaques (Macaca mulatta), using shotgun sequencing data (Gibbs et al 2007).…”