Genetic Conflict Shapes Centromeres and Heterochromatin

描述(由申请人提供)： 染色体分离是一个必不可少的过程。确保染色体适当分离的关键染色体部位是着丝粒，它结合了微管，在减数分裂和有丝分裂期间将染色体或染色单体分开。着丝粒功能对染色体分离至关重要。着丝粒缺陷可能导致不孕不育、肿瘤发生和唐氏综合症等出生缺陷。尽管染色体分离过程是保守的，着丝粒DNA序列在密切相关的物种内部和之间都进化得很快。此外，与着丝粒DNA结合以组装微管招募运动中枢的基本着丝粒蛋白也进化迅速。着丝粒蛋白和DNA的这种快速进化与人们的期望形成鲜明对比，即它们应该高度保守，以维持基本功能，其基本机制在所有真核生物中都是保守的。我们提出，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染色体之间的竞争，即四种减数分裂产物中只有一种被选为卵原核。着丝粒驱动的有害后果，特别是在男性减数分裂中，选择了着丝粒和异染色质蛋白的快速进化，以平息着丝粒驱动或其有害影响。使用一种结合了进化遗传学和细胞生物学的见解的方法，我们建议在果蝇物种中测试这种遗传冲突模型。我们将进一步测试着丝粒蛋白的快速进化和遗传创新对染色体分离的基本过程的功能影响。

DESCRIPTION (provided by applicant): 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 infertility, tumorigenesis and birth defects like Down's syndrome. Despite the conservation of the chromosome segregation process, centromeric DNA sequences evolve rapidly, both within and between closely related species. Moreover, essential centromeric proteins, which bind centromeric DNA to assemble microtubule-recruiting kinetochores, also evolve rapidly. This rapid evolution of both centromeric proteins and DNA is in sharp contrast to the expectation that they should be highly conserved to maintain essential function, whose basic mechanism has been conserved in all eukaryotes. We have 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. Deleterious consequences of centromere-drive, especially in male meiosis, selects for the rapid evolution of centromeric and heterochromatin proteins, to quell drive or its deleterious effects. Using an approach that combines insights from evolutionary genetics and cell biology, we propose to test this model of genetic conflict in Drosophila species. We will further test the functional consequences of rapid evolution and genetic innovation in centromeric proteins, on the fundamental process of chromosome segregation.