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Molecular and evolutionary characterization of male recombination and its reversal in the D. nasuta species subgroup

D. nasuta 物种亚群雄性重组及其逆转的分子和进化特征

基本信息

批准号：
10251849
负责人：
Heng Chin Kevin Wei
金额：
$ 9.22万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-02 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10251849
关键词：
Address Alleles Aneuploidy Behavior Biochemical CRISPR/Cas technology Chromosome Segregation Chromosomes Coupled Disease Dissection Down Syndrome Drosophila genus Electron Microscopy Engineering Ensure Evaluation Evolution Female Filament GTP-Binding Protein alpha Subunits, Gs Gene Expression Profile Genes Genetic Genetic Materials Genetic Polymorphism Genetic Recombination Genetic Variation Genome Genome Scan Haplotypes Homologous Gene Human Hybrids Immunofluorescence Immunologic Immunoprecipitation Individual Mammals Maps Mass Spectrum Analysis Meiosis Meiotic Recombination Microscopy Modeling Modification Molecular Mutation Natural Selections Organism Ovary Pathway interactions Phenotype Phylogenetic Analysis Process Protein C Proteins Reagent Recombinants Resolution Ribosomes Scanning Scheme Sex Chromosomes Sex Ratio Sister Son Source Spontaneous abortion Structure Subgroup Synaptonemal Complex Tertiary Protein Structure Testing Testis Transgenic Organisms Y Chromosome base causal variant chromosome fusion cost dimorphism fitness fly genome sequencing genomic tools insight interest male novel offspring pressure sample fixation sex sexual dimorphism transcriptome transmission process whole genome

项目摘要

PROJECT SUMMARY/ABSTRACT Meiotic recombination is the exchange of genetic material between homologous chromosomes and is universally found in sexually reproducing organisms. By creating novel allelic combinations through chromosomal crossovers, meiotic recombination promotes genetic diversity and the efficacy of natural selection. When recombination is absent, like on the Y chromosome, deleterious mutations irreversibly accumulate in a process known as degeneration. The synaptonemal complex, which is required for the formation of crossovers, tethers homologues together and facilitates their proper disjunction in meiosis. Disruptions to to the process result in aneuploidy, which is the leading cause of Down syndrome and spontaneous abortions. Despite its essential functions, aspects of meiotic recombination are unexpectedly prone to change. Many genes involved are rapidly evolving under positive selection and, similarly, recombination rate can drastically differ between closely related species, and even between sexes. In fact, many distinct taxa, including Drosophila, lost the ability to recombine in males altogether, a.k.a. male achiasmy. While much of the mechanistic details are well characterized particularly in model species, it remains unclear as to why recombination is so labile. This proposal aims to address this question by focusing on D. nasuta, which, unique among Drosophila, has male recombination, and its sister species D. albomicans, which reverted to male achiasmy less than 100 thousand years ago. The reversal in D. albomicans occurred after fixation of two chromosomal fusions creating a pair of young neo-sex chromosomes. I previously showed that, prior to the reversal, male recombination produced multiple neo-Y haplotypes that now have different extent of degeneration. These two species offer an unique opportunity to determine the genetic, evolutionary, and molecular bases underlying the transition to and from achiasmy. I propose to identify the causal locus underlying the reversal to male achiasmy in D. albomicans, combining genomic tools and a classical phenotype mapping scheme (Aim 1). Candidates will be confirmed via transgenic manipulation with CRIPSR-Cas9. I will investigate the evolution of known genes involved in meiotic recombination in these two as well as closely related species, reasoning that male recombination in D. nasuta likely required activation of and adaptive modifications to the existing recombination machineries (Aim2). The resulting molecular and mechanistic changes during D. nasuta male meiosis will then be characterized with high resolution microscopy (Aim 2). Finally, I will determine the evolutionary pressure causing the reversal to male achiasmy in D. albomicans by testing the hypothesis that male recombination incurs a fitness cost due to the presence of the neo-Y chromosome (Aim 3). Execution of these aims will provide significant insight on the causes and consequences underlying the dichotomy between functional conservation and lability of recombination.

项目总结/文摘