Department of Biological Sciences, University of Denver, Denver, CO 80208, USA.
Division of Biological Sciences, University of Montana, Missoula, MT 59812, USA.
G3 (Bethesda). 2022 Feb 4;12(2). doi: 10.1093/g3journal/jkab407.
Hybrid sterility is a complex phenotype that can result from the breakdown of spermatogenesis at multiple developmental stages. Here, we disentangle two proposed hybrid male sterility mechanisms in the house mice, Mus musculus domesticus and M. m. musculus, by comparing patterns of gene expression in sterile F1 hybrids from a reciprocal cross. We found that hybrid males from both cross directions showed disrupted X chromosome expression during prophase of meiosis I consistent with a loss of meiotic sex chromosome inactivation (MSCI) and Prdm9-associated sterility, but that the degree of disruption was greater in mice with an M. m. musculus X chromosome consistent with previous studies. During postmeiotic development, gene expression on the X chromosome was only disrupted in one cross direction, suggesting that misexpression at this later stage was genotype-specific and not a simple downstream consequence of MSCI disruption which was observed in both reciprocal crosses. Instead, disrupted postmeiotic expression may depend on the magnitude of earlier disrupted MSCI, or the disruption of particular X-linked genes or gene networks. Alternatively, only hybrids with a potential deficit of Sly copies, a Y-linked ampliconic gene family, showed overexpression in postmeiotic cells, consistent with a previously proposed model of antagonistic coevolution between the X- and Y-linked ampliconic genes contributing to disrupted expression late in spermatogenesis. The relative contributions of these two regulatory mechanisms and their impact on sterility phenotypes await further study. Our results further support the hypothesis that X-linked hybrid sterility in house mice has a variable genetic basis, and that genotype-specific disruption of gene regulation contributes to overexpression of the X chromosome at different stages of development. Overall, these findings underscore the critical role of epigenetic regulation of the X chromosome during spermatogenesis and suggest that these processes are prone to disruption in hybrids.
杂种不育是一种复杂的表型，可能是由于精子发生在多个发育阶段的破裂而导致的。在这里，我们通过比较来自相互交叉的不育 F1 杂种的基因表达模式，解开了家鼠 Mus musculus domesticus 和 M. m. musculus 中两种提出的杂种雄性不育机制。我们发现，来自两个交叉方向的杂种雄性在减数分裂 I 前期表现出 X 染色体表达中断，与减数分裂性染色体失活（MSCI）和 Prdm9 相关的不育一致，但在具有 M. m. musculus X 染色体的小鼠中，中断程度更大，这与之前的研究一致。在减数分裂后发育过程中，X 染色体上的基因表达仅在一个交叉方向上受到干扰，这表明这种较晚阶段的错误表达是基因型特异性的，而不是 MSCI 中断的简单下游后果，这种中断在两个相互交叉的方向都观察到。相反，减数分裂后表达的中断可能取决于早期 MSCI 中断的程度，或者是特定的 X 连锁基因或基因网络的中断。或者，只有具有 Sly 拷贝（Y 连锁扩增基因家族）潜在缺陷的杂种，在减数分裂后细胞中表现出过表达，这与之前提出的 X 和 Y 连锁扩增基因之间的拮抗共同进化模型一致，该模型有助于在精子发生后期破坏表达。这两种调节机制的相对贡献及其对不育表型的影响有待进一步研究。我们的研究结果进一步支持了家鼠 X 连锁杂种不育具有可变遗传基础的假设，并且基因调控的基因型特异性中断导致 X 染色体在发育的不同阶段过度表达。总的来说，这些发现强调了 X 染色体在精子发生过程中表观遗传调控的关键作用，并表明这些过程在杂种中容易受到破坏。
