Beyond sex determination: the evolution and function of Y chromosomes

超越性别决定：Y 染色体的进化和功能

• 批准号: 2211661
• 负责人: Polly Campbell
• 金额: $ 148.68万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2211661&HistoricalAwards=false
• 关键词: Beyond; sex; determination; evolution; function

Early in the 180 million-year history of mammalian sex chromosomes, the Y chromosome lost most of its genes. Thus, surviving ancestral genes are highly conserved across most mammals. However, recent evolution on the Y is remarkably dynamic. The handful of fully annotated mammalian Y chromosomes all feature lineage-specific genes acquired from other parts of the genome. This regenerative property of Y chromosomes was not anticipated by theory and the evolutionary drivers are poorly understood. To fill this knowledge gap, the research will produce Y chromosome assemblies and multi-tissue transcriptomes for eight closely related species of rodents with unusually high rates of sex chromosome evolution. These data will be used to test hypotheses about the functions of Y-linked genes. Further, the work will investigate the selective forces that promote gene acquisition and survival. The research will be integrated into inquiry-based undergraduate curriculum at two minority-serving institutions. It will also provide mentored research experiences for undergraduates recruited through programs targeting under-represented groups. The results of this research will shed new light on the function and short-term evolution of Y chromosomes. This project will also promote engagement and retention of under-represented minorities in science, and provide training opportunities for students.The research will use long read sequencing technologies and optical mapping to produce telomere-to-telomere Y chromosome assemblies for a group of voles (genus, Microtus). This group includes M. oregoni, a species in which both sexes carry full complements of Y-derived genes. Multi-tissue gene expression atlases will be produced for each species. The atlases will be generated using a combination of long and short read transcriptomes and single cell sequencing. Aim 1 will use a comparative framework to understand gene acquisition, molecular evolution, and gene loss on Microtus Y chromosomes. The first aim will also evaluate functional associations and patterns of copy number amplification. Aim 2 has two goals. First, it will test the dominant paradigm for mammalian Y-linked gene function, under which surviving ancestral genes are broadly expressed regulators that compensate for X chromosome hemizygosity, whereas genes acquired from other parts of the genome are specialized for spermatogenesis. Second, aim 2 will test for expression patterns consistent with alternative drivers of Y-acquired gene survival in Microtus. Aim 3 will leverage the unique sex chromosome system of M. oregoni for two purposes. One, to re-evaluate the dominant paradigm for Y chromosome gene function by analyzing the effects of sex and X chromosome dosage on Y-derived gene expression. Two, to test the longstanding prediction that sex-limited chromosomes accumulate genes with sexually antagonistic effects in the shared genome.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在哺乳动物性染色体1.8亿年历史的早期，Y染色体丢失了大部分基因。因此，存活下来的祖先基因在大多数哺乳动物中是高度保守的。然而，Y轴最近的演变是非常动态的。少数完全注释的哺乳动物Y染色体都具有从基因组其他部分获得的谱系特异性基因。Y染色体的这种再生特性在理论上是没有预料到的，而且对进化的驱动因素也知之甚少。为了填补这一知识空白，该研究将为8种密切相关的啮齿动物物种产生Y染色体组装和多组织转录组，这些啮齿动物具有异常高的性染色体进化率。这些数据将被用来检验关于Y连锁基因功能的假设。此外，这项工作将调查促进基因获得和生存的选择力。这项研究将纳入两个少数民族服务机构的探究式本科课程。它还将为通过针对代表性不足群体的项目招募的本科生提供指导性研究经验。这项研究的结果将为Y染色体的功能和短期进化提供新的线索。该项目还将促进在科学领域代表性不足的少数群体的参与和保留，并为学生提供培训机会。该研究将使用长读测序技术和光学作图，为一组田鼠（田鼠属）生产端粒到端粒Y染色体组装。这个组包括M。牛至，一个物种，其中两性携带Y衍生基因的完整补充。将为每个物种制作多组织基因表达图谱。将使用长和短读段转录组和单细胞测序的组合生成图谱。目的1将使用一个比较框架来了解田鼠Y染色体上的基因获得、分子进化和基因丢失。第一个目标还将评估拷贝数扩增的功能关联和模式。目标2有两个目标。首先，它将测试哺乳动物Y连锁基因功能的主导范式，在这种范式下，幸存的祖先基因是广泛表达的调节因子，可以补偿X染色体半合子，而从基因组其他部分获得的基因则专门用于精子发生。第二，目标2将测试与Y-获得性基因存活的替代驱动因素一致的表达模式。目标3将利用M.牛油果有两个用途第一，通过分析性别和X染色体剂量对Y染色体基因表达的影响，重新评估Y染色体基因功能的主导范式。第二，验证长期以来的预测，即性别限制的染色体在共享基因组中积累了具有性拮抗效应的基因。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。