Investigating the evolutionary genetics and genomic consequences of sex-ratio meiotic drive in Drosophila

项目摘要 真核生物基因组包含多种进化上的“自私”遗传元件(SGE)，它们获得了 以牺牲它们的主营运营商为代价的传输优势。SGE倾向于使用两个宽泛中的一个 策略：相对于宿主基因组过度复制(例如，转座元件)或扭曲公平的孟德尔 传递(例如，减数分裂驱动元件)。性染色体特别容易受到入侵 和减数分裂驱动元件的积累，通过扭曲X和Y染色体的传递 选择性杀死精子，偏向后代性别比。这种“性别比驱动”会加剧进化冲突。 X连锁、Y连锁和常染色体上的驱动基因和驱动抑制因子之间的关系。分子 这种由驾车调停的冲突反复爆发所引发的军备竞赛可能会产生深远的影响 对男性生育力、人口学的影响(包括单性恋人口的潜在风险 物种灭绝)、基因组进化和物种形成。了解遗传学，分子机制， 因此，进化动力学和性别比驱动的基因组后果是至关重要的。 在这里，我们建议研究一种最近演变的性别比驱动和抑制系统，然后， 正如在分子军备竞赛动态下所预期的那样，在三个密切相关的物种中迅速多样化 果蝇--拟果蝇、毛果果蝇和果蝇。我们之前的工作表明，虽然这些 物种分化了约250Kya，今天由于大量的遗传不亲和性而被生殖隔离， 尽管如此，这三个国家之间还是出现了一些基因流动。我们发现所谓的温特斯性爱- 比率驱动系统是X连锁的、卫星DNA相关的DOX样样(DXL)驱动基因家族的一部分 拷贝数扩增，序列多样化。这些DXL基因编码预测的DNA结合 精子特异组蛋白，我们预测它会差异化地干扰X-和Y-染色体的染色质重塑 精子发生过程中的精子细胞原核。此外，我们发现每个物种都有两个 产生发夹RNA的常染色体抑制基因产生内源性小干扰RNA (EsiRNAs)被预测专门沉默DXL基因家族的不同子集。最后，我们 发现一些DXL基因和抑制子显示出最近强烈的群体遗传特征 选择和种间基因流动。我们的研究项目旨在结合实验遗传学， 分子生物学、第三代测序和进化基因组学方法剖析DXL驱动因素- HpRNA抑制物相互作用；确定DXL编码的组蛋白和 它对Y染色体序列内容进化的意义；并推断其进化史 DXL介导的分子军备竞赛的动力学，包括它对杂交进化的影响 不育性和种间基因流动。

Project Summary Eukaryotic genomes contain a diversity of evolutionarily “selfish” genetic elements (SGEs) that obtain transmission advantages at the expense of their host carriers. SGEs tend to use one of two broad strategies: over-replicate relative to the host genome (e.g., transposable elements) or distort fair Mendelian transmission (e.g., meiotic drive elements). Sex chromosomes are especially susceptible to the invasion and accumulation of meiotic drive elements that, by distorting X versus Y chromosome transmission via selective sperm-killing, bias progeny sex ratios. Such “sex-ratio drive” can potentiate evolutionary conflicts of interest between drive genes and drive-suppressors at X-linked, Y-linked, and autosomal loci. Molecular arms races arising from recurrent bouts of such drive-mediated conflict can have far reaching consequences for male fertility, for demography (including the potential risk of unisexual population extinction), for genome evolution, and for speciation. Understanding the genetics, molecular mechanisms, evolutionary dynamics, and genomic consequences of sex-ratio drive is therefore of paramount importance. Here we propose to investigate a system of sex-ratio drive and suppression that evolved recently and then, as expected under molecular arms race dynamics, rapidly diversified among three closely related species of Drosophila— D. simulans, D. mauritiana, and D. sechellia. Our previous work revealed that, while these species diverged ~250 Kya and are today reproductively isolated by numerous genetic incompatibilities, some gene flow has nevertheless occurred among all three. We discovered that the so-called Winters sex- ratio drive system is part of a family of X-linked, satellite DNA-associated, Dox-like (Dxl) drive genes that amplified in copy number and diversified in sequence. These Dxl genes encode predicted DNA-binding sperm-specific histones, which we predict differentially disrupt chromatin remodeling of X- versus Y-bearing spermatid pronuclei during spermiogenesis. Furthermore, we found that each species possesses two hairpin RNA-producing autosomal suppressor genes that produce endogenous small interfering RNAs (esiRNAs) predicted to specialize in the silencing of different subsets of the Dxl gene family. Finally, we discovered that some Dxl genes and suppressors show population genetic signatures of strong recent selection and interspecies gene flow. Our research project aims to combine experimental genetics, molecular biology, third-generation sequencing, and evolutionary genomics methods to dissect Dxl driver- hpRNA suppressor interactions; to determine the genomic binding targets of the Dxl-encoded histones and its implications for the evolution of Y chromosome sequence content; and to infer the evolutionary history and dynamics of Dxl-mediated molecular arms races, including its implications for the evolution of hybrid sterility and interspecific gene flow.