Faster-X adaptive protein evolution in house mice

Abstract

The causes of the large effect of the X chromosome in reproductive isolation and speciation have long been debated. The faster-X hypothesis predicts that X-linked loci are expected to have higher rates of adaptive evolution than autosomal loci if new beneficial mutations are on average recessive. Reproductive isolation should therefore evolve faster when contributing loci are located on the X chromosome. In this study, we have analyzed genome-wide nucleotide polymorphism data from the house mouse subspecies Mus musculus castaneus and nucleotide divergence from Mus famulus and Rattus norvegicus to compare rates of adaptive evolution for autosomal and X-linked protein-coding genes. We found significantly faster adaptive evolution for X-linked loci, particularly for genes with expression in male-specific tissues, but autosomal and X-linked genes with expression in female-specific tissues evolve at similar rates. We also estimated rates of adaptive evolution for genes expressed during spermatogenesis and found that X-linked genes that escape meiotic sex chromosome inactivation (MSCI) show rapid adaptive evolution. Our results suggest that faster-X adaptive evolution is either due to net recessivity of new advantageous mutations or due to a special gene content of the X chromosome, which regulates male function and spermatogenesis. We discuss how our results help to explain the large effect of the X chromosome in speciation.

Keywords: placeholder.

Figure 1

The site-frequency spectra (SFS) for nonsynonymous and synonymous site classes of autosomal and X-linked genes. Shading indicates the expected SFS for an equilibrium population under a neutral Wright–Fisher model of evolution. The SFSs are for non-CpG prone sites.

Figure 2

The distribution of fitness effects of new nonsynonymous mutations binned into four classes of effects for autosomal and X-linked genes. The estimates are for non-CpG prone sites; 95% confidence intervals were generated by bootstrapping by gene.

Figure 3

Molecular evolution (Α) and breadth of expression (Β) of genes that have male- or female-specific expression and non-sex-specific expression. (Α) Estimates for d_N/d_S, α, and ω_a were calculated using M. famulus as the ougroup and were corrected for the contribution of polymorphism to divergence. Error bars are 95% confidence intervals (CIs) obtained by bootstrapping by gene. Two-tailed bootstrap tests were performed to compare d_N/d_S, α, and ω_a estimates with the autosomal average (indicated by the dashed line) and between autosomal and X-linked genes of each class. Asterisks indicate significance for the comparison to the autosomal average (*, P < 0.05; **, P < 0.01). (B) Boxes indicate 25th and 75th percentiles of the distribution of τ and whiskers are ∼95% CIs. Solid line within boxes indicates the median τ and notches are ∼95% CIs for the median. Dashed line indicates the genomic average τ. A Mann–Whitney U-test was performed to compare median τ between autosomal and X-linked genes of each class. (A and B) Signs indicate significance for the comparisons between autosomal and X-linked genes (one sign, P < 0.05; two signs, P < 0.01).

Figure 4

Expression pattern (A) and molecular evolution (B) of three groups of genes expressed during spermatogenesis. (A) Group A are genes that are expressed exclusively premeiotically, group B are genes that are expressed during premeiosis and postmeiosis, and group C are genes that are expressed exclusively postmeiotically. Boxes indicate 25th and 75th percentiles of log₂ expression intensity and whiskers are ∼95% CIs. Solid line within boxes indicates median expression intensity and notches are ∼95% CIs for the median. The dashed line indicates the expression intensity threshold that was used to define a gene as being expressed. (B) Estimates for d_N/d_S, α, and ω_a for group A, group B, and group C. d_N/d_S, α, and ω_a were calculated by using M. famulus as the ougroup and were corrected for the contribution of polymorphism to divergence. Error bars are 95% CIs obtained by bootstrapping by gene. Two-tailed bootstrap tests were performed to compare d_N/d_S, α, and ω_a estimates with the autosomal average (indicated by the dashed line) and between autosomal and X-linked genes of each class. Asterisks indicate significance for the comparison to the autosomal average (*, P < 0.05; **, P < 0.01). Signs indicate significance for the comparisons between autosomal and X-linked genes (one sign, P < 0.05; two signs, P < 0.01).