Abstract

The classical definition posits hybrid sterility as a phenomenon when two parental taxa each of which is fertile produce a hybrid that is sterile. The first hybrid sterility gene in vertebrates, Prdm9, coding for a histone methyltransferase, was identified in crosses between two laboratory mouse strains derived from Mus mus musculus and M. m. domesticus subspecies. The unique function of PRDM9 protein in the initiation of meiotic recombination led to the discovery of the basic molecular mechanism of hybrid sterility in laboratory crosses. However, the role of this protein as a component of reproductive barrier outside the laboratory model remained unclear. Here, we show that the Prdm9 allelic incompatibilities represent the primary cause of reduced fertility in intersubspecific hybrids between M. m. musculus and M. m. domesticus including 16 musculus and domesticus wild-derived strains. Disruption of fertility phenotypes correlated with the rate of failure of synapsis between homologous chromosomes in meiosis I and with early meiotic arrest. All phenotypes were restored to normal when the domesticus Prdm9dom² allele was substituted with the Prdm9dom2H humanized variant. To conclude, our data show for the first time the male infertility of wild-derived musculus and domesticus subspecies F1 hybrids controlled by Prdm9 as the major hybrid sterility gene. The impairment of fertility surrogates, testes weight and sperm count, correlated with increasing difficulties of meiotic synapsis of homologous chromosomes and with meiotic arrest, which we suppose reflect the increasing asymmetry of PRDM9-dependent DNA double-strand breaks.

中文翻译：

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Prdm9 家鼠杂交雄性不育中亚种间的相互作用。

 抽象的

经典定义将杂交不育视为一种现象，即两个亲本类群均具有可育性，产生不育的杂交体。脊椎动物中第一个杂交不育基因Prdm9编码组蛋白甲基转移酶，是在源自Mus mus musculus和M. m.的两种实验室小鼠品系之间的杂交中发现的。家养亚种。 PRDM9蛋白在减数分裂重组启动中的独特功能导致实验室杂交中杂种不育的基本分子机制的发现。然而，这种蛋白质作为实验室模型之外的生殖屏障组成部分的作用仍不清楚。在这里，我们表明Prdm9等位基因不相容性代表了M. m.之间亚种间杂种育性降低的主要原因。肌肉和M. m。家畜包括 16 种家畜和家畜野生品系。生育表型的破坏与减数分裂 I 中同源染色体之间的突触失败率以及早期减数分裂停滞相关。当家畜 Prdm9dom ²等位基因被Prdm9dom2H人源化变体取代时，所有表型均恢复正常。总而言之，我们的数据首次显示了由Prdm9作为主要杂交不育基因控制的野生家蝇和家蝇亚种 F1 杂交体的雄性不育。 生育力替代物、睾丸重量和精子数量的损害与同源染色体减数分裂突触的增加困难以及减数分裂停滞相关，我们认为这反映了PRDM9依赖性DNA双链断裂的不对称性增加。