Sex-Differential Selection and the Evolution of X Inactivation Strategies

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.X染色体失活（X inactivation）——即每个雌性体细胞中一条X染色体拷贝发生转录沉默——在兽亚纲哺乳动物（therian mammals）中普遍存在，但不同物种间对沉默哪一条X染色体的选择存在显著差异。X染色体失活策略的谱系跨度极广，从严格父源X染色体失活（strictly paternally inherited X inactivation, PXI）——使雌性所有母源等位基因呈现单倍体状态——到无偏倚随机X染色体失活（unbiased random X inactivation, RXI）——使每个雌性组织中母源与父源等位基因的表达水平趋于均衡。然而，目前学界仍未明确能够解释这一X染色体失活策略多样性的潜在进化机制。本研究针对X染色体失活的进化开展了理论种群遗传学分析，专门考量显性效应、连锁关系、重组情况以及性别差异化选择等条件，分别如何影响X染色体失活的进化轨迹。研究结果显示，等位基因显性效应与性别差异化选择之间的单一关键互作，可选择出宽泛且连续的X染色体失活策略谱系，其中包括母源与父源X染色体间不均等的失活比例。只要对雌性适合度有害的等位基因具备足够的隐性特性，随机X染色体失活（RXI）就比完全父源X染色体失活（PXI）更受选择青睐；而当适合度变异存在性拮抗（sexually antagonistic）特性——即对雌性有害的等位基因对雄性有益——时，相较于仅对两性均有害的变异，随机X染色体失活进化的判定标准要严格得多。从完全父源X染色体失活（PXI）到随机X染色体失活（RXI）的进化转变，通常还会以雄性适合度下降为代价，提升雌性的平均相对适合度。本研究结果为预测和解读X连锁基因的全染色体表达进化提供了理论框架，并引出若干具有实用价值的预测方向，有望推动未来针对等位基因特异性基因表达变异的相关研究。