Genetic Conflict Shapes Centromeres and Heterochromatin

项目摘要 染色体分离是一个必不可少的过程。关键的染色体位点， 确保染色体正确分离的是着丝粒，它结合微管 在减数分裂和有丝分裂过程中将染色体或染色单体拉开。着丝粒 因此，功能对于染色体分离至关重要。有缺陷的着丝粒会导致 非整倍体、不孕症和先天缺陷，如唐氏综合症。尽管 染色体分离过程的保守性，着丝粒蛋白如CenH3， 结合着丝粒DNA组装微管募集动粒， 在近缘物种之间迅速传播。它们的快速进化是出乎意料的， 危及染色体分离过程的精确性。我们先前提出， 这种快速进化的发生是由于“着丝粒驱动”，即，之间的竞争 在女性减数分裂过程中，只有四个减数分裂产物中的一个是染色体， 被选为卵原核。使用的方法结合了 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 我建议在果蝇物种中测试这种遗传冲突模型。此外，基于 在我们发现CenH3在果蝇物种中重复的基础上，我们将测试 体细胞与种系着丝粒功能是否具有不同的功能 限制，这是最容易解决的基因复制和专业化的 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.