Genetic Conflict Shapes Centromeres and Heterochromatin

项目总结 染色体分离是一个必不可少的过程。关键的染色体位置 确保染色体的适当分离是着丝粒，它绑定了微管 在减数分裂和有丝分裂期间将染色体或染色单体分开。着丝粒 因此，功能对染色体分离至关重要。有缺陷的着丝粒可能导致 到非整倍体、不孕不育和唐氏综合症之类的出生缺陷。尽管 染色体分离过程的保守性，着丝粒蛋白如CenH3， 它结合着丝粒DNA来组装微管招募运动中心，进化 在亲缘关系密切的物种之间迅速传播。它们的快速进化是意想不到的，可能 危及染色体分离过程的保真度。我们之前曾提出 这种快速进化是由于“着丝粒驱动”，即 在雌性减数分裂过程中，四个减数分裂产物中只有一个是 被选为卵原核。使用一种结合了以下见解的方法 进化遗传学和细胞生物学，以及最先进的基因组工程工具，我们 建议在果蝇物种中测试这种遗传冲突模型。此外，基于 关于我们在果蝇物种中发现的CenH3反复重复的情况，我们将测试 体细胞着丝粒和生殖系着丝粒功能是否具有不同的功能 限制，这是最容易通过基因复制和特化解决的 CenH3基因。

PROJECT SUMMARY Chromosome segregation is an essential process. The key chromosomal sites that ensure proper segregation of chromosomes are centromeres, which bind microtubules that pull chromosomes or chromatids apart during meiosis and mitosis. Centromere function is thus essential for chromosome segregation. Defective centromeres can lead to aneuploidy, infertility, and birth defects like Down’s syndrome. Despite the conservation of the chromosome segregation process, centromeric proteins like CenH3, which bind centromeric DNA to assemble microtubule-recruiting kinetochores, evolve rapidly between closely related species. Their rapid evolution is unexpected and could imperil the fidelity of the chromosome segregation process. We previously proposed that this rapid evolution occurs due to ‘centromere-drive’, i.e., competition between chromosomes during female meiosis, in which only one of four meiotic products is chosen to be the egg pronucleus. Using an approach that combines insights from evolutionary genetics and cell biology, and state-of-the-art genome engineering tools, we propose to test this model of genetic conflict in Drosophila species. Furthermore, based on our finding of recurrent duplication of CenH3 in Drosophila species, we will test whether somatic versus germline centromeric functions have different functional constraints, which are easiest to resolve via gene duplication and specialization of CenH3 genes.