Genetic Conflict Shapes Centromeres and Heterochromatin

遗传冲突塑造着丝粒和异染色质

• 批准号: 8888585
• 负责人: HARMIT S MALIK
• 金额: $ 35.3万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8888585
• 关键词: Address; Adopted; Affect; Aneuploidy; Animals; Automobile Driving; Binding; Biological; Biological Process; Cell division; Cellular biology; Centromere; Chimeric Proteins; Chromatids; Chromosome Segregation; Chromosomes; Complex; Conflict (Psychology); Congenital Abnormality; DNA; DNA Sequence; DNA-Binding Proteins; Defect; Disease; Down Syndrome; Drosophila genus; Embryo; Engineering; Ensure; Essential Genes; Eukaryota; Evolution; Female; Fertility; Functional disorder; Gene Duplication; Genes; Genetic; Genetic Models; Genetic screening method; Health; Heterochromatin; Histone H3; Human; Impairment; Infertility; Kinetochores; Lead; Light; Maintenance; Malignant Neoplasms; Mediating; Meiosis; Microtubules; Mimulus; Mitosis; Modeling; Mus; Plants; Positioning Attribute; Process; Proteins; RNA Interference; Recruitment Activity; Recurrence; Role; Satellite DNA; Shapes; Site; Testing; Tissues; Variant; Yeasts; base; cost; daughter cell; design; egg; expectation; fly; genetic evolution; genetic information; in vivo; innovation; insight; interdisciplinary approach; interest; male; novel; parity; public health relevance; transmission process; tumorigenesis

 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.

 描述（由申请人提供）： 染色体分离是一个必不可少的过程。确保染色体正确分离的关键染色体位点是着丝粒，它结合微管，在减数分裂和有丝分裂期间将染色体或染色单体拉开。因此，着丝粒功能是染色体分离所必需的。有缺陷的着丝粒会导致不孕、肿瘤和先天缺陷，如唐氏综合症。尽管染色体分离过程是保守的，但着丝粒DNA序列在密切相关的物种内和物种之间都迅速进化。此外，结合着丝粒DNA组装微管募集动粒的必需着丝粒蛋白也迅速进化。着丝粒蛋白和DNA的这种快速进化与期望它们应该高度保守以维持基本功能形成鲜明对比，其基本机制在所有真核生物中都是保守的。我们已经提出，这种快速进化的发生是由于“着丝粒驱动”，即，在雌性减数分裂过程中染色体之间的竞争，其中四种减数分裂产物中只有一种被选择为卵原核。着丝粒驱动的有害后果，特别是在男性减数分裂中，选择快速进化的着丝粒和异染色质蛋白，以平息驱动或其有害影响。使用的方法，结合进化遗传学和细胞生物学的见解，我们建议测试果蝇物种的遗传冲突的这种模式。我们将进一步测试着丝粒蛋白质的快速进化和遗传创新的功能后果，对染色体分离的基本过程。