Beyond sex determination: the evolution and function of Y chromosomes

在哺乳动物性染色体1.8亿年历史的早期，Y染色体失去了大部分基因。因此，存活下来的祖先基因在大多数哺乳动物中都是高度保守的。然而，最近Y轴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的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并没有被理论预测到，进化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种具有异常高性染色体进化率的密切相关的啮齿动物物种制作Y染色体组装和多组织转录组。这些数据将用于检验关于y连锁基因功能的假设。此外，这项工作将调查促进基因获取和生存的选择力量。该研究将被整合到两所少数族裔服务机构的探究式本科课程中。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研究经验。这一研究结果将为Y染色体的功能和短期进化提供新的线索。该项目还将促进代表性不足的少数民族对科学的参与和保留，并为学生提供培训机会。这项研究将使用长读测序技术和光学测绘技术为一组田鼠（鼠属）产生端粒到端粒的Y染色体组合。这一群体包括俄勒冈m.o oregoni，这是一种两性都携带完全互补的y源基因的物种。将为每个物种制作多组织基因表达图谱。图谱将使用长、短读转录组和单细胞测序相结合的方法生成。目的1将使用比较框架来了解鼠Y染色体上的基因获取、分子进化和基因丢失。第一个目的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模式，在这种模式下，幸存的祖先基因是广泛表达的调节因子，补偿X染色体的半合子性，而从基因组的其他部分获得的基因专门用于精子发生。其次，目的2将测试与鼠y获得性基因存活的其他驱动因素一致的表达模式。目的3将利用俄勒冈分枝杆菌独特的性染色体系统为两个目的。第一，通过分析性别和X染色体剂量对Y源性基因表达的影响，重新评估Y染色体基因功能的主导范式。二是验证长期以来的预测，即性别限制染色体在共享基因组中积累具有性对抗作用的基因。该奖项反映了美国国家科学基金会的法定使命，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。

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.