Laboratory of Mouse Molecular Genetics, Institute of Molecular Genetics, Czech Academy of Sciences, Vestec 252 50, Czech Republic.
Central Laboratory of Bioinformatics, CEITEC-Central European Institute of Technology, Masaryk University, Brno 625 00, Czech Republic.
Genetics. 2022 Aug 30;222(1). doi: 10.1093/genetics/iyac116.
Hybrid sterility contributes to speciation by preventing gene flow between related taxa. Prdm9, the first and only hybrid male sterility gene known in vertebrates, predetermines the sites of recombination between homologous chromosomes and their synapsis in early meiotic prophase. The asymmetric binding of PRDM9 to heterosubspecific homologs of Mus musculus musculus × Mus musculus domesticus F1 hybrids and increase of PRDM9-independent DNA double-strand break hotspots results indificult- to- repair double-strand breaks, incomplete synapsis of homologous chromosomes, and meiotic arrest at the first meiotic prophase. Here, we show that Prdm9 behaves as a major hybrid male sterility gene in mice outside the Mus musculus musculus × Mus musculus domesticus F1 hybrids, in the genomes composed of Mus musculus castaneus and Mus musculus musculus chromosomes segregating on the Mus musculus domesticus background. The Prdm9cst/dom2 (castaneus/domesticus) allelic combination secures meiotic synapsis, testes weight, and sperm count within physiological limits, while the Prdm9msc1/dom2 (musculus/domesticus) males show a range of fertility impairment. Out of 5 quantitative trait loci contributing to the Prdm9msc1/dom2-related infertility, 4 control either meiotic synapsis or fertility phenotypes and 1 controls both, synapsis, and fertility. Whole-genome genotyping of individual chromosomes showed preferential involvement of nonrecombinant musculus chromosomes in asynapsis in accordance with the chromosomal character of hybrid male sterility. Moreover, we show that the overall asynapsis rate can be estimated solely from the genotype of individual males by scoring the effect of nonrecombinant musculus chromosomes. Prdm9-controlled hybrid male sterility represents an example of genetic architecture of hybrid male sterility consisting of genic and chromosomal components.
杂种不育通过阻止相关分类群之间的基因流动来促进物种形成。Prdm9 是脊椎动物中已知的第一个也是唯一一个杂种雄性不育基因，它预先确定了同源染色体之间的重组位点及其在早期减数分裂前期的联会。PRDM9 在异亚种同源物上的不对称结合，以及 PRDM9 不依赖的 DNA 双链断裂热点的增加，导致难以修复的双链断裂、同源染色体不完全联会以及减数分裂停滞在第一次减数分裂前期。在这里，我们表明 Prdm9 在 Mus musculus musculus × Mus musculus domesticus F1 杂种之外的小鼠中表现为主要的杂种雄性不育基因，在由 Mus musculus castaneus 和 Mus musculus musculus 染色体组成的基因组中，这些染色体在 Mus musculus domesticus 背景下分离。Prdm9cst/dom2（castaneus/domesticus）等位基因组合确保了减数分裂联会、睾丸重量和精子计数在生理范围内，而 Prdm9msc1/dom2（musculus/domesticus）雄性则表现出一系列生育能力受损。在导致 Prdm9msc1/dom2 相关不育的 5 个数量性状位点中，有 4 个控制减数分裂联会或生育表型，1 个控制联会和生育。个别染色体的全基因组基因分型显示，非重组的 musculus 染色体优先参与不联会，这与杂种雄性不育的染色体特征一致。此外，我们表明，通过对非重组 musculus 染色体的基因型进行评分，可以仅从个体雄性的基因型来估计整体不联会率。Prdm9 控制的杂种雄性不育代表了由基因和染色体成分组成的杂种雄性不育遗传结构的一个例子。
