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

研究果蝇性别比减数分裂驱动的进化遗传学和基因组后果

• 批准号: 10733936
• 负责人: DAVEN C PRESGRAVES
• 金额: $ 30.8万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-22 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10733936
• 关键词: Alleles; Binding; Conflict (Psychology); Conflict of Interest; DNA; DNA Binding; DNA Binding Domain; DNA Sequence; DNA Transposable Elements; Data; Demography; Drosophila genus; Elements; Enhancers; Evolution; Experimental Genetics; Extinction; Family; Fishes; Gene Amplification; Gene Family; Genes; Genetic; Genetic Polymorphism; Genetic Recombination; Genetic study; Genome; Genomic Instability; Genomics; Histones; Human; Hybrids; Infertility; Insecta; Invaded; Knock-out; Link; Mammals; Mediating; Meiosis; Methods; Molecular; Molecular Biology; Mutation; Nucleotides; Organism; Phenotype; Plants; Population; Population Genetics; Predisposition; Process; Production; Protamines; RNA; RNA Interference; Recording of previous events; Recurrence; Reproduction; Research; Research Project Grants; Resistance; Risk; Role; Satellite DNA; Selfish Genes; Sex Chromosomes; Sex Ratio; Shapes; Side; Small Interfering RNA; Spermatids; Spermatogenesis; Spermiogenesis; Sterility; Suppressor Genes; System; Testing; Third Generation Sequencing; Work; X Chromosome; Y Chromosome; arms race; autosome; chromatin remodeling; experimental study; fungus; genetic signature; male; male fertility; reproductive; sperm cell; transmission process

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.

项目摘要 真核生物基因组包含多样性的进化“自私”遗传元件（SGE）， 以牺牲其主运营商为代价来获得传输优势。SGE倾向于使用两种广泛的 策略：相对于宿主基因组过度复制（例如，转座因子）或扭曲公平孟德尔 传输（例如，减数分裂驱动元件）。性染色体特别容易受到入侵 以及减数分裂驱动元件的积累，通过扭曲X与Y染色体的传递， 选择性杀死精子，使后代性别比例产生偏差。这种“性别比例驱动”可能会加剧进化冲突 感兴趣的驱动基因和驱动抑制基因之间的X-连锁，Y-连锁，和常染色体基因座。分子 由这种驱动调解的冲突反复发生而引起的军备竞赛可能产生深远的影响， 对男性生育力、人口统计学（包括单性群体的潜在风险）的影响 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例驱动的基因组后果至关重要。 在这里，我们打算研究一个性别比例驱动和抑制的系统，它是最近进化的， 正如在分子军备竞赛动力学下所预期的那样，在三个密切相关的物种之间迅速多样化， 果蝇D. simulans、D. mauritiana和D. sechellia。我们以前的工作表明，虽然这些 物种分歧约250 Kya和今天生殖隔离的许多遗传不相容性， 然而，在这三个国家之间都发生了一些基因流动。我们发现所谓的温特斯性爱 比率驱动系统是X连锁、卫星DNA相关、Dox样（Dxl）驱动基因家族的一部分， 拷贝数扩增且序列多样化。这些Dxl基因编码预测的DNA结合 精子特异性组蛋白，我们预测差异破坏染色质重塑X与Y轴承 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 在一些实施方案中，siRNA（esiRNA）被预测专门用于Dxl基因家族的不同子集的沉默。最后我们 发现一些Dxl基因和抑制基因显示出强烈的近期群体遗传特征， 选择和物种间基因流动。我们的研究项目旨在将联合收割机实验遗传学， 分子生物学、第三代测序和进化基因组学方法来剖析Dxl驱动程序， hpRNA抑制因子相互作用;以确定Dxl编码的组蛋白的基因组结合靶标， 它对Y染色体序列内容进化的影响;并推断进化历史 Dxl介导的分子军备竞赛的动力学，包括其对杂种进化的影响， 不育性和种间基因流动。