Heterozygous inversion breakpoints suppress meiotic crossovers by altering recombination repair outcomes.
Heterozygous inversion breakpoints suppress meiotic crossovers by altering recombination repair outcomes.
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DOI：
10.1371/journal.pgen.1010702
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发表时间：
2023-04
期刊：
影响因子：
4.5
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中科院分区：
文献类型：
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杂合染色体倒位抑制倒位内减数分裂交换（CO）的形成，这可能是因为它们导致产生不活配子的总染色体重排。有趣的是，CO也严重减少，在附近的区域，但反转断点以外，即使在这些地区的CO不会导致重排。我们对为什么CO在倒位断点之外被抑制的机械理解受到缺乏这些区域非交换基因转换（NCOGC）频率数据的限制。为了解决这个关键的差距，我们绘制了罕见的CO和NCOGC事件的位置和频率，这些事件发生在D.黑腹菌我们创建了全同胞野生型和倒位原种，并在两种原种的同线区域中恢复了CO和NCOGC，使我们能够直接比较重组事件的速率和分布。我们发现，CO以外的近端反转断点分布在一个距离依赖的方式，最强的抑制附近的反转断点。我们发现，NCOGCs均匀地发生在整个染色体，重要的是，不抑制附近的反转断点。我们提出了一个模型，在该模型中，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，以距离依赖的方式通过反转断点抑制CO。我们认为，在联会复合体和染色体配对的微妙变化可能会导致不稳定的同源物之间的相互作用，在重组过程中，允许NCOGC的形成，但不CO的形成。减数分裂是用于产生遗传多样性和减少配子中基因组拷贝数的特化细胞周期。成功的减数分裂需要同源染色体配对和重组以形成交换，这是正确的染色体分离所必需的。然而，染色体重排称为倒位，它颠倒了同源染色体上基因的顺序，抑制了交叉。虽然这一现象已经被研究了100年，但关于防止交叉发生的机制仍有很多未知之处。在我们目前的工作中，我们表明，这些杂合倒位通过改变重组的调节来抑制附近但在重排边界之外的交叉。
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. Meiosis is the specialized cell cycle used to generate genetic diversity and reduce the genome copy number in gametes. Successful meiosis requires homologous chromosomes to pair and recombine to form crossovers, which are necessary for proper chromosome segregation. However, chromosome rearrangements called inversions that reverse the order of genes on one of the homologous chromosomes suppress crossovers. While this phenomenon has been studied for 100 years, much is still unknown about the mechanisms that prevent crossovers from occurring. In our current work, we show that these heterozygous inversions suppress crossovers nearby but outside of the rearrangement boundaries by altering the regulation of recombination.
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DOI：
10.1073/pnas.0500172102
发表时间：
2005-03-22
影响因子：
11.1
作者：
Anderson, LK;Royer, SM;Hawley, RS
通讯作者：
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影响因子：
5.8
作者：
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影响因子：
4.5
作者：
Kulathinal, Rob J.;Stevison, Laurie S.;Noor, Mohamed A. F.
通讯作者：
Noor, Mohamed A. F.
影响因子：
3.3
作者：
Machado, Carlos A.;Haselkorn, Tamara S.;Noor, Mohamed A. F.
通讯作者：
Noor, Mohamed A. F.
果蝇果蝇重组率自然变异的遗传结构。
影响因子：
4.5
作者：
Hunter CM;Huang W;Mackay TF;Singh ND
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Singh ND