Sex-differential selection and the evolution of X inactivation strategies

Abstract

X inactivation--the transcriptional silencing of one X chromosome copy per female somatic cell--is universal among therian mammals, yet the choice of which X to silence exhibits considerable variation among species. X inactivation strategies can range from strict paternally inherited X inactivation (PXI), which renders females haploid for all maternally inherited alleles, to unbiased random X inactivation (RXI), which equalizes expression of maternally and paternally inherited alleles in each female tissue. However, the underlying evolutionary processes that might account for this observed diversity of X inactivation strategies remain unclear. We present a theoretical population genetic analysis of X inactivation evolution and specifically consider how conditions of dominance, linkage, recombination, and sex-differential selection each influence evolutionary trajectories of X inactivation. The results indicate that a single, critical interaction between allelic dominance and sex-differential selection can select for a broad and continuous range of X inactivation strategies, including unequal rates of inactivation between maternally and paternally inherited X chromosomes. RXI is favored over complete PXI as long as alleles deleterious to female fitness are sufficiently recessive, and the criteria for RXI evolution is considerably more restrictive when fitness variation is sexually antagonistic (i.e., alleles deleterious to females are beneficial to males) relative to variation that is deleterious to both sexes. Evolutionary transitions from PXI to RXI also generally increase mean relative female fitness at the expense of decreased male fitness. These results provide a theoretical framework for predicting and interpreting the evolution of chromosome-wide expression of X-linked genes and lead to several useful predictions that could motivate future studies of allele-specific gene expression variation.

Figure 1. Relationship between X inactivation rule and parent-of-origin dominance coefficients (h_mat , h_pat ; see Table 1 ).

Results are based on the power function for female fitness, w(x) = 1−x^ks_f, where x represents the proportion of female cells expressing the A ₁ allele, s_f is the haploid or homozygous selection coefficient, h is the degree of masking (equivalent to a dominance coefficient of A ₁) in individuals practicing unbiased RXI (ξ ₁₁ = ½), and k = −ln(2)/ln(h). For additional details, see the main text. The figure is modified from, and inspired by, Figure 1a of .

Figure 2. Criteria for the evolution of RXI.

Black curves are based on eq. (3) for the mutation-selection balance model of genetic variation (in which case, the x-axis refers to the female selection coefficient, s_f). The gray curve is based on eq. (4) for sexually antagonistic alleles maintained by balancing selection (here, the x-axis refers to the male selection coefficient: t_m). The area above each curve represents parameter space where unbiased RXI is not favored over PXI. RXI is favored under the complementary parameter space below each curve.

Figure 3. Sexually antagonistic fitness variation and the change in mean fitness following the evolution of RXI.

In an ancestral population with PXI, and segregating for a sexually antagonistic balanced polymorphism, unbiased RXI is favored and may evolve when h<h_crit = (1−t_m)/(2−t_m). Following such an evolutionary transition, the male-beneficial/female-detrimental allele approaches a new equilibrium frequency, and mean fitness per sex evolves to a new equilibrium.

Figure 4. Sex-differential selection favors the evolution of biased RXI.

Black curves are based on eq. (8) for the mutation-selection balance model of genetic variation; diamonds are based on numerical evaluation of the more exact eq. (7). Gray curves are based on eq. (9) for sexually antagonistic alleles maintained by balancing selection. Results for the mutation-selection balance case assume equal male and female selection coefficients (s_m = s_f). Biases are further accentuated when s_m>s_f; biases may be dampened or reversed when s_m<s_f.