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

项目摘要/摘要 减数分裂重组是同源染色体之间遗传物质的交换，是普遍存在的 在有性繁殖有机体中发现。通过染色体创造新的等位基因组合 交叉，减数分裂重组促进了遗传多样性和自然选择的有效性。什么时候 没有重组，就像在Y染色体上一样，有害的突变在一个过程中不可逆转地积累 这就是所谓的退化。联会复合体，这是形成交叉，系绳所必需的 在减数分裂过程中，它们相互同源并促进它们的适当分离。对流程的中断会导致 非整倍体，这是唐氏综合症和自然流产的主要原因。尽管它是必不可少的 减数分裂重组的功能、方面都出人意料地容易发生变化。许多涉及到的基因正在迅速地 正向选择下的进化和类似地，重组率可以在密切相关的 物种，甚至在性别之间。事实上，许多不同的分类群，包括果蝇，失去了重组的能力 在所有男性中，也就是。男性成就障碍。虽然许多机械性的细节都有很好的特点 尤其是在模式物种中，为什么重组如此不稳定，目前还不清楚。 这项提案旨在通过关注D.nasuta来解决这个问题，D.nasuta是果蝇中独一无二的，它有 雄性重组，及其姊妹种白纹藻，在不到100岁时恢复为雄性成就 一千年前。白纹伊氏菌的逆转发生在两条染色体的融合形成 一对年轻的新性别染色体。我之前的研究表明，在逆转之前，男性重组 产生了多种neo-Y单倍型，这些单倍型现在有不同程度的退化。这两个物种提供了一种 独特的机会来确定向和的转变背后的遗传、进化和分子基础 从成就感。我建议确定白纹伊蚊逆转为男性共济失调的原因， 结合基因组工具和经典的表型作图方案(目标1)。候选人将通过以下途径确认 用CRIPSR-Cas9进行转基因操作。我将研究涉及减数分裂的已知基因的进化。 在这两个物种以及近缘物种中的重组，推测鼻毛虫的雄性重组 可能需要对现有重组机器(AIM2)进行激活和适应性修改。这个 由此导致的分子和机制的变化，在减数分裂过程中，将以高 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 通过检验雄性重组会导致适应成本的假设，在白纹伊蚊中取得成就，这是因为 存在neo-Y染色体(目标3)。这些目标的实现将对原因提供重要的洞察 以及在功能守恒和重组不稳定之间的二分法背后的后果。

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.