Genetic Mechanisms of Reproductive Isolation in House Mice
Summary
The process of reproductive isolation in house mice (Mus musculus) hinges on genetic incompatibilities that arise during divergence of subspecies. In natural hybrid zones between M. m. musculus and M. m. domesticus, hybrids often suffer male‐limited sterility, a barrier maintained by negative interactions among loci. Central to this barrier is Prdm9, a histone methyltransferase that directs the location of meiotic double‐strand breaks and recombination hotspots. Divergent Prdm9 alleles and an X‐linked sterility region (commonly termed Hstx2) interact to disrupt meiotic chromosome synapsis, triggering asynapsis of homologues and arrest of spermatogenesis. Additional autosomal modifiers further modulate recombination rates and fertility outcomes, revealing a multilocus network of Dobzhansky–Muller incompatibilities. Cytological defects such as failure of synaptonemal-complex formation, mispairing of sex chromosomes and widespread transcriptional misregulation during spermatogenesis underpin hybrid male sterility. Together, these genetic and cellular phenomena establish a robust post‐zygotic barrier that has become a paradigmatic model for understanding speciation in mammals, with implications for fertility research and the design of laboratory crosses.
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Technical terms
Dobzhansky–Muller incompatibility: Negative epistatic interaction between alleles at two or more loci that reduces hybrid fitness.
Prdm9: A zinc-finger histone methyltransferase that specifies the positions of meiotic recombination hotspots.
Hybrid sterility locus (Hstx2/Meir1): An X-linked genomic region that interacts with Prdm9 to cause male-limited meiotic arrest.
Meiotic asynapsis: Failure of homologous chromosomes to align and form the synaptonemal complex during prophase I.
Synaptonemal complex: A proteinaceous structure that holds homologous chromosomes together to permit crossover formation.
Haldane’s rule: The tendency for the heterogametic sex to exhibit sterility or inviability in interspecific hybrids.
References
- Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse. PLOS Genetics (2016).
- Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice. eLife (2018).
- Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions. eLife (2014).
- Genomic Networks of Hybrid Sterility. PLOS Genetics (2014).
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