Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
PLoS Genet. 2013;9(12):e1003963. doi: 10.1371/journal.pgen.1003963. Epub 2013 Dec 5.
Reduction in ploidy to generate haploid gametes during sexual reproduction is accomplished by the specialized cell division program of meiosis. Pairing between homologous chromosomes and assembly of the synaptonemal complex at their interface (synapsis) represent intermediate steps in the meiotic program that are essential to form crossover recombination-based linkages between homologs, which in turn enable segregation of the homologs to opposite poles at the meiosis I division. Here, we challenge the mechanisms of pairing and synapsis during C. elegans meiosis by disrupting the normal 1:1 correspondence between homologs through karyotype manipulation. Using a combination of cytological tools, including S-phase labeling to specifically identify X chromosome territories in highly synchronous cohorts of nuclei and 3D rendering to visualize meiotic chromosome structures and organization, our analysis of trisomic (triplo-X) and polyploid meiosis provides insight into the principles governing pairing and synapsis and how the meiotic program is "wired" to maximize successful sexual reproduction. We show that chromosomes sort into homologous groups regardless of chromosome number, then preferentially achieve pairwise synapsis during a period of active chromosome mobilization. Further, comparisons of synapsis configurations in triplo-X germ cells that are proficient or defective for initiating recombination suggest a role for recombination in restricting chromosomal interactions to a pairwise state. Increased numbers of homologs prolong markers of the chromosome mobilization phase and/or boost germline apoptosis, consistent with triggering quality control mechanisms that promote resolution of synapsis problems and/or cull meiocytes containing synapsis defects. However, we also uncover evidence for the existence of mechanisms that "mask" defects, thus allowing resumption of prophase progression and survival of germ cells despite some asynapsis. We propose that coupling of saturable masking mechanisms with stringent quality controls maximizes meiotic success by making progression and survival dependent on achieving a level of synapsis sufficient for crossover formation without requiring perfect synapsis.
在有性生殖过程中,通过减数分裂的特化细胞分裂程序将二倍体降低为单倍体配子。同源染色体的配对和它们接口处联会复合体(synapsis)的组装是减数分裂程序的中间步骤,对于形成同源之间基于交叉重组的连接至关重要,这反过来又使同源体在减数分裂 I 分裂时分离到相对的两极。在这里,我们通过染色体操作破坏同源体之间的正常 1:1 对应关系,从而挑战线虫减数分裂中的配对和联会机制。使用细胞遗传学工具的组合,包括 S 期标记以特异性识别高度同步的核群体中的 X 染色体区室,以及 3D 渲染以可视化减数分裂染色体结构和组织,我们对三体(triplo-X)和多倍体减数分裂的分析提供了对配对和联会的原则的深入了解,以及减数分裂程序如何“布线”以最大程度地成功进行有性生殖。我们表明,染色体无论染色体数量如何,都会分类成同源组,然后在活跃的染色体动员期间优先实现成对的联会。此外,对能够或不能起始重组的 triplo-X 生殖细胞的联会构型的比较表明,重组在将染色体相互作用限制为成对状态方面起着作用。同源体数量的增加会延长染色体动员阶段的标记,或者增加生殖细胞凋亡,这与触发质量控制机制一致,该机制可促进联会问题的解决和/或剔除含有联会缺陷的减数分裂细胞。然而,我们还发现了存在“掩盖”缺陷的机制的证据,从而允许联会问题得到解决并继续进行前期进展,即使存在一些联会缺陷,生殖细胞也能存活。我们提出,通过将饱和掩蔽机制与严格的质量控制相结合,使进展和存活取决于达到足以形成交叉的联会水平,而无需完美的联会,从而最大程度地提高减数分裂的成功率。