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The contribution of sex chromosome conflict to disrupted spermatogenesis in hybrid house mice

Kopania, Emily E K, Watson, Eleanor M, Rathje, Claudia C., Skinner, Benjamin M, Ellis, Peter J.I., Larson, Erica L., Good, Jeffrey M. (2022) The contribution of sex chromosome conflict to disrupted spermatogenesis in hybrid house mice. Genetics, 222 (4). ISSN 1943-2631. (doi:10.1093/genetics/iyac151) (KAR id:97464)


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 Mus musculus F1 hybrids, but variation in sterility phenotypes suggests a more complex genetic basis. Additionally, X-Y 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 X-Y 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 X-Y 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 X-Y gene copy number imbalance. Y-chromosome introgression did result in subfertility phenotypes and disrupted expression of several autosomal genes in mice with an otherwise non-hybrid genomic background, suggesting that Y-linked incompatibilities contribute to reproductive barriers, but likely not as a direct consequence of X-Y 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.

Item Type: Article
DOI/Identification number: 10.1093/genetics/iyac151
Additional information: For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Uncontrolled keywords: speciation, intragenomic conflict, ampliconic genes, hybrid male sterility, testis expression, FACS, sex chromosomes
Subjects: Q Science > QL Zoology
Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Divisions: Divisions > Division of Natural Sciences > Centre for Interdisciplinary Studies of Reproduction
Divisions > Division of Natural Sciences > Biosciences
Funders: National Science Foundation (
Eunice Kennedy Shriver Center (
Biotechnology and Biological Sciences Research Council (
Leverhulme Trust (
University of Essex (
Depositing User: Peter Ellis
Date Deposited: 17 Oct 2022 08:16 UTC
Last Modified: 13 Oct 2023 22:09 UTC
Resource URI: (The current URI for this page, for reference purposes)

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Rathje, Claudia C..

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Ellis, Peter J.I..

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