Polly Campbell - US grants

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.<br/><br/>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.<br/><br/>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.