Department of Biology, Case Western Reserve University, Cleveland, Ohio, United States of America.
Division of Genetic Medicine, Department of Pediatrics, University of Washington and Seattle Children's Hospital, Seattle, Washington, United States of America.
PLoS Genet. 2023 Apr 13;19(4):e1010702. doi: 10.1371/journal.pgen.1010702. eCollection 2023 Apr.
Heterozygous chromosome inversions suppress meiotic crossover (CO) formation within an inversion, potentially because they lead to gross chromosome rearrangements that produce inviable gametes. Interestingly, COs are also severely reduced in regions nearby but outside of inversion breakpoints even though COs in these regions do not result in rearrangements. Our mechanistic understanding of why COs are suppressed outside of inversion breakpoints is limited by a lack of data on the frequency of noncrossover gene conversions (NCOGCs) in these regions. To address this critical gap, we mapped the location and frequency of rare CO and NCOGC events that occurred outside of the dl-49 chrX inversion in D. melanogaster. We created full-sibling wildtype and inversion stocks and recovered COs and NCOGCs in the syntenic regions of both stocks, allowing us to directly compare rates and distributions of recombination events. We show that COs outside of the proximal inversion breakpoint are distributed in a distance-dependent manner, with strongest suppression near the inversion breakpoint. We find that NCOGCs occur evenly throughout the chromosome and, importantly, are not suppressed near inversion breakpoints. We propose a model in which COs are suppressed by inversion breakpoints in a distance-dependent manner through mechanisms that influence DNA double-strand break repair outcome but not double-strand break formation. We suggest that subtle changes in the synaptonemal complex and chromosome pairing might lead to unstable interhomolog interactions during recombination that permits NCOGC formation but not CO formation.
杂合染色体倒位抑制倒位内部的减数分裂交叉（CO）形成，这可能是因为它们导致了严重的染色体重排，从而产生了不可育的配子。有趣的是，即使在这些区域的 CO 不会导致重排，它们也会严重减少倒位断点附近但在其之外的区域的 CO。我们对为什么 CO 在倒位断点之外被抑制的机制理解受到这些区域中非交叉基因转换（NCOGC）频率缺乏数据的限制。为了解决这个关键的差距，我们绘制了 D. melanogaster 中 dl-49 chrX 倒位之外稀有 CO 和 NCOGC 事件的位置和频率。我们创建了全同胞野生型和倒位品系，并在这两个品系的同源区域中恢复了 CO 和 NCOGC，使我们能够直接比较重组事件的速率和分布。我们表明，近端倒位断点之外的 CO 以依赖距离的方式分布，在倒位断点附近抑制最强。我们发现 NCOGC 均匀地发生在整个染色体上，并且重要的是，在倒位断点附近不受抑制。我们提出了一个模型，其中 CO 以依赖距离的方式被倒位断点抑制，通过影响 DNA 双链断裂修复结果但不影响双链断裂形成的机制。我们认为，联会复合体和染色体配对的细微变化可能导致在重组过程中不稳定的同源物相互作用，从而允许 NCOGC 形成而不是 CO 形成。
