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

项目总结/摘要 减数分裂重组是同源染色体之间遗传物质的交换， 发现于有性繁殖的生物体中。通过创造新的等位基因组合， 通过杂交，减数分裂重组促进了遗传多样性和自然选择的效力。当 如果没有重组，就像Y染色体上一样，有害的突变在一个过程中不可逆地积累， 称为退化。联会复合体，这是形成交叉，栓系所必需的 同源物在一起，并促进它们在减数分裂中的适当分离。对过程的干扰导致 非整倍体，这是唐氏综合症和自然流产的主要原因。尽管其基本 功能，减数分裂重组的方面出乎意料地倾向于改变。许多相关基因迅速 在正选择下进化，同样，密切相关的基因之间的重组率也会有很大差异。 物种之间，甚至性别之间。事实上，许多不同的分类群，包括果蝇，失去了重组的能力 在男性中也就是说男性视交叉虽然许多机械细节都很好地描述了 特别是在模式物种中，为什么重组如此不稳定仍不清楚。 本建议旨在解决这一问题，重点是D。nasuta，在果蝇中是独一无二的， 雄性重组，其姊妹种D. Albomicans，在100以下恢复为男性视交叉 千年前D. Albomicans发生在两个染色体融合固定后， 一对年轻的新性别染色体我之前指出，在逆转之前，雄性重组 产生了多个neo-Y单倍型，现在有不同程度的退化。这两个物种提供了一个 独特的机会，以确定遗传，进化和分子基础的过渡， 关于achiasmy我建议确定的因果轨迹背后的逆转男性交叉在D。阿尔伯马人， 结合基因组工具和经典的表型作图方案（Aim 1）。候选人将通过 用CRIPSR-Cas9进行转基因操作。我将研究已知的参与减数分裂的基因的进化 这两个以及密切相关的物种中的雄性重组，推理D. nasuta 可能需要激活和适应性修改现有的重组机制（Aim 2）。的 导致D. nasuta雄性减数分裂的特征是高 分辨率显微镜（Aim 2）。最后，我将确定导致男性逆转的进化压力 D.通过测试假设，男性重组招致健身成本，由于 新Y染色体的存在（Aim 3）。这些目标的实现将提供关于原因的重要见解 以及功能保守性和重组不稳定性之间二分法的潜在后果。

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.