Incompatibilities on the sex chromosomes are important in the evolution of hybrid male sterility, but the evolutionary forces underlying this phenomenon are unclear. House mice (Mus musculus) lineages have provided powerful models for understanding the genetic basis of hybrid male sterility. X chromosome–autosome interactions cause strong incompatibilities in M. musculus F1 hybrids, but variation in sterility phenotypes suggests a more complex genetic basis. In addition, XY chromosome conflict has resulted in rapid expansions of ampliconic genes with dosage-dependent expression that is essential to spermatogenesis. Here, we evaluated the contribution of XY lineage mismatch to male fertility and stage-specific gene expression in hybrid mice. We performed backcrosses between two house mouse subspecies to generate reciprocal Y-introgression strains and used these strains to test the effects of XY mismatch in hybrids. Our transcriptome analyses of sorted spermatid cells revealed widespread overexpression of the X chromosome in sterile F1 hybrids independent of Y chromosome subspecies origin. Thus, postmeiotic overexpression of the X chromosome in sterile F1 mouse hybrids is likely a downstream consequence of disrupted meiotic X-inactivation rather than XY gene copy number imbalance. Y chromosome introgression did result in subfertility phenotypes and disrupted expression of several autosomal genes in mice with an otherwise nonhybrid genomic background, suggesting that Y-linked incompatibilities contribute to reproductive barriers, but likely not as a direct consequence of XY conflict. Collectively, these findings suggest that rapid sex chromosome gene family evolution driven by genomic conflict has not resulted in strong male reproductive barriers between these subspecies of house mice.
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.
more » « less- Award ID(s):
- 2012041
- NSF-PAR ID:
- 10363564
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- G3 Genes|Genomes|Genetics
- Volume:
- 12
- Issue:
- 2
- ISSN:
- 2160-1836
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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