Essential roles for RNAi/hpRNAs to resolve intragenomic conflicts in the male germline

RNAi/hpRNA 在解决雄性种系基因组内冲突中的重要作用

• 批准号: 10467212
• 负责人: Eric C Lai
• 金额: $ 59.92万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-03 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10467212
• 关键词: ATAC-seq; Antidotes; Arthropods; Binding; Biochemical; Biological; Biology; Breeding; Catalysis; Cellular Assay; Chromatin; Chromosomes; Conflict (Psychology); Data; Defect; Dependence; Drosophila genus; Elements; Evolution; Exhibits; Family; Fertility; Foundations; Gene Amplification; Gene Family; Genes; Genetic; Genetic Transcription; Genome; Genomics; Hand; Histones; Impairment; Individual; Insecta; Invertebrates; Investigation; Knock-out; Laws; Lead; Left; Legal patent; Life; Link; Logic; Maintenance; Male Sterility; Mammals; Maps; Meiosis; Modeling; Molecular; Mus; Nuclear Family; Pathway interactions; Phenotype; Play; Population; Protamines; Proteins; Proteome; Proteomics; RNA; RNA Interference; Recurrence; Repression; Role; Selfish Genes; Sex Bias; Sex Chromosomes; Sex Ratio; Small Interfering RNA; Small RNA; Son; Source; Spermatogenesis; Spermiogenesis; Sterility; System; Taxonomy; Testing; Testis; Tissues; Work; causal variant; comparative genomics; fitness; gene product; genetic element; in vivo; innovation; insight; male; mouse model; multidisciplinary; mutant; next generation; novel; pandemic disease; preservation; pressure; reproductive; sex; sperm cell; tool; transcriptome; transcriptome sequencing; transmission process

PROJECT ABSTRACT Intragenomic conflicts are fueled by rapidly evolving selfish genetic elements, which emerge intrinsically within genomes. If left unchecked, these can be disastrous to the individual and/or the population. Thus, such conflicts induce strong pressures to innovate opposing mechanisms of repression. This is patently manifest in paradoxical meiotic drive systems, in which the wildtype activities of selfish genes can have deleterious consequences to bias the sex ratio of progeny (typically eliminating males), or to induce frank sterility. However, relatively little is known about the molecular mechanisms of meiotic drive genes and their control. Our recent work provides first evidence that related, recently-evolved, sex-biasing and sterility-inducing systems in the non-model fruitfly D. simulans are suppressed by endogenous siRNA loci. This provides a unique foundation to study how meiotic drive loci are tamed at the post-transcriptional level. Although little is generally known about the biochemical function of selfish meiotic drive loci, our data support testable models in which these D. simulans distorter gene products may interfere with chromatin packing in sperm. Finally, we will examine the broader evolutionary implications for how endogenous siRNAs may unlock maps of intragenomic conflicts in multiple Drosophila species, and examine a rationale for analogous molecular battles during mammalian meiosis. Our multidisciplinary investigations will elucidate mechanisms that link tissue-specific de novo gene activity and small RNAs with rapid genome dynamics that may impose the reproductive isolation of individuals, potentially early steps on the path towards speciation.

项目摘要 快速进化的自私遗传因素加剧了基因组内的冲突， 它们本质上出现在基因组中。如果不加以检查，这些可能会对 个人和/或群体。因此，这种冲突引发了强大的压力 创新对立的压制机制。这一点明显地体现在自相矛盾的 减数分裂驱动系统，其中自私基因的野生型活动可以 对子代性别比产生偏见的有害后果(通常是剔除雄性)， 或导致坦率的不育。然而，对这种分子的了解相对较少。 减数分裂驱动基因的机制及其调控。我们最近的工作提供了第一个 有证据表明，相关的，最近进化的，性别偏见和不育诱导系统 非模型模拟果蝇被内源性siRNA基因座抑制。这提供了 研究减数分裂驱动基因如何在转录后驯化的独特基础 水平。尽管人们对自私减数分裂的生化功能知之甚少 驱动基因，我们的数据支持可测试模型，在这些模型中，这些模拟D 产品可能会干扰精子中的染色质包装。最后，我们将研究 内源性siRNA如何解锁 多个果蝇物种间的基因组内冲突，并研究了 哺乳动物减数分裂过程中类似的分子战。我们的多学科 研究将阐明将组织特异性从头基因活性联系起来的机制 和具有快速基因组动态的小RNA，这可能会造成生殖隔离 对于个体来说，可能是物种形成道路上的早期步骤。