Synaptonemal Complex-Deficient Drosophila melanogaster Females Exhibit Rare DSB Repair Events, Recurrent Copy-Number Variation, and an Increased Rate of de Novo Transposable Element Movement
Synaptonemal Complex-Deficient Drosophila melanogaster Females Exhibit Rare DSB Repair Events, Recurrent Copy-Number Variation, and an Increased Rate of de Novo Transposable Element Movement
复制标题
DOI：
10.1534/g3.119.400853
复制
发表时间：
2020-02-01
影响因子：
2.6
通讯作者：
Miller, Danny E.
中科院分区：
文献类型：
--
作者：
Miller, Danny E.
遗传稳定性取决于各种染色体结构的维持和DNA断裂的精确修复。在减数分裂期间，在前期I中产生的程序性双链断裂（DSB）通常作为基因转换或交换而被修复。DSB也可以通过其他机制产生，例如转座因子（TE）的移动，这也必须解决。这些DNA损伤的不正确修复可导致突变、拷贝数变化、易位和/或非整倍体配子。在黑腹果蝇中，与大多数生物一样，减数分裂DSB修复发生在一种称为联会复合体（SC）的快速进化的多蛋白结构的存在下。在这里，全基因组测序是用来调查的命运减数分裂DSB在D。黑腹果蝇突变体雌性缺乏功能性SC，以测定从头CNV形成，并检查SC在果蝇转座因子运动中的作用。这些数据表明，在没有SC的情况下，拷贝数变异仍然发生，并且通过基因转换进行的减数分裂DSB修复很少发生。值得注意的是，在两个不同遗传背景的不相关个体中观察到856-脱氢酶从头CNV，并且与先前野生型研究中回收的CNV相同，这表明在果蝇中发生大CNV的复发形成。此外，新的TE插入率显着高于野生型的两个SC突变体中的一个测试，表明SC蛋白可能有助于调节TE的运动和插入的基因组。总的来说，这项研究为SC在基因组稳定性中所起的作用提供了新的见解，并为SC蛋白的序列而不是结构迅速演变提供了线索。
Genetic stability depends on the maintenance of a variety of chromosome structures and the precise repair of DNA breaks. During meiosis, programmed double-strand breaks (DSBs) made in prophase I are normally repaired as gene conversions or crossovers. DSBs can also be made by other mechanisms, such as the movement of transposable elements (TEs), which must also be resolved. Incorrect repair of these DNA lesions can lead to mutations, copy-number changes, translocations, and/or aneuploid gametes. In Drosophila melanogaster, as in most organisms, meiotic DSB repair occurs in the presence of a rapidly evolving multiprotein structure called the synaptonemal complex (SC). Here, whole-genome sequencing is used to investigate the fate of meiotic DSBs in D. melanogaster mutant females lacking functional SC, to assay for de novo CNV formation, and to examine the role of the SC in transposable element movement in flies. The data indicate that, in the absence of SC, copy-number variation still occurs and meiotic DSB repair by gene conversion occurs infrequently. Remarkably, an 856-kilobase de novo CNV was observed in two unrelated individuals of different genetic backgrounds and was identical to a CNV recovered in a previous wild-type study, suggesting that recurrent formation of large CNVs occurs in Drosophila. In addition, the rate of novel TE insertion was markedly higher than wild type in one of two SC mutants tested, suggesting that SC proteins may contribute to the regulation of TE movement and insertion in the genome. Overall, this study provides novel insight into the role that the SC plays in genome stability and provides clues as to why the sequence, but not structure, of SC proteins is rapidly evolving.