Meiotic Consequences of Genetic Divergence Across the Murine Pseudoautosomal Region.
Meiotic Consequences of Genetic Divergence Across the Murine Pseudoautosomal Region.
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DOI：
10.1534/genetics.116.189092
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发表时间：
2017-03
期刊：
影响因子：
3.3
通讯作者：
Dumont BL
中科院分区：
文献类型：
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作者：
Dumont BL
减数分裂过程中单倍体配子的产生依赖于同源性驱动的配对、联会和重组过程。在哺乳动物异配子性染色体上，这些关键的减数分裂活动局限于假常染色体区（PAR），这是X和Y染色体之间具有近乎完美序列同源性的短区域。尽管它对减数分裂的重要性已经确立，但PAR正在迅速发展，这就提出了一个问题，即如何适当地缓冲X/Y分离以防止同源性破坏突变的积累。在这里，我研究了两个具有可繁殖性家鼠亚种（Mus musculus domesticus和Mus musculus domesticus）中PAR进化和功能的相互作用，这两个亚种的特征是结构不同的PAR。M.栗色的使用细胞遗传学方法可视化减数分裂的性染色体，我表明，亚种间F1杂种怀有粗线期精母细胞与unsynapsed性染色体的频率增加。这种高比率的突触不连部分是由于在前期I完成之前突触联合的过早释放。此外，我表明，当性染色体在亚种间杂种突触，重组减少整个配对区域。总之，这些减数分裂缺陷折磨了近50%的F1代精母细胞，并导致减数分裂细胞凋亡增加。尽管公然破坏减数分裂程序，一个子集的精母细胞完成减数分裂和亚种间F1雄性保持生育能力。这些发现揭示了性染色体进化的减数分裂限制，并为解决这个功能重要的基因座的快速进化所引起的悖论提供了初步线索。
The production of haploid gametes during meiosis is dependent on the homology-driven processes of pairing, synapsis, and recombination. On the mammalian heterogametic sex chromosomes, these key meiotic activities are confined to the pseudoautosomal region (PAR), a short region of near-perfect sequence homology between the X and Y chromosomes. Despite its established importance for meiosis, the PAR is rapidly evolving, raising the question of how proper X/Y segregation is buffered against the accumulation of homology-disrupting mutations. Here, I investigate the interplay of PAR evolution and function in two interfertile house mouse subspecies characterized by structurally divergent PARs, Mus musculus domesticus and M. m. castaneus. Using cytogenetic methods to visualize the sex chromosomes at meiosis, I show that intersubspecific F1 hybrids harbor an increased frequency of pachytene spermatocytes with unsynapsed sex chromosomes. This high rate of asynapsis is due, in part, to the premature release of synaptic associations prior to completion of prophase I. Further, I show that when sex chromosomes do synapse in intersubspecific hybrids, recombination is reduced across the paired region. Together, these meiotic defects afflict ∼50% of spermatocytes from F1 hybrids and lead to increased apoptosis in meiotically dividing cells. Despite flagrant disruption of the meiotic program, a subset of spermatocytes complete meiosis and intersubspecific F1 males remain fertile. These findings cast light on the meiotic constraints that shape sex chromosome evolution and offer initial clues to resolve the paradox raised by the rapid evolution of this functionally significant locus.