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: 10617394
• 负责人: Eric C Lai
• 金额: $ 57.99万
• 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/10617394
• 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; Equilibrium; Evolution; Exhibits; Family; Fertility; Foundations; Gene Amplification; Gene Family; Genes; Genetic; Genome; Genomics; Hand; Histones; Impairment; Individual; Insecta; Invertebrates; Investigation; Knock-out; Laws; Left; Legal patent; Life; Link; Logic; Maintenance; Male Sterility; Male Sterilizations; Mammals; Maps; Meiosis; Modeling; Molecular; Mus; Nuclear Family; Paper; 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; posttranscriptional; 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 快速进化的自私基因元件助长了基因组内的冲突， 这些基因在基因组中自然产生。如果不加以控制，这些可能是灾难性的， 个人和/或群体。因此，这种冲突产生了强大的压力， 创新对立的镇压机制。这显然是自相矛盾的 减数分裂驱动系统，其中自私基因的野生型活动可以 造成后代性别比例偏差的有害后果（通常排除雄性）， 或者导致不育然而，相对而言， 减数分裂驱动基因及其控制的机制。我们最近的工作首先提供了 证据表明，相关的，最近进化的，性别偏见和不育诱导系统中， 非模式果蝇D. simulans被内源siRNA基因座抑制。这提供 一个独特的基础，研究如何减数分裂驱动基因座是驯服在转录后 水平尽管人们对自私减数分裂的生化功能知之甚少， 驱动位点，我们的数据支持可测试的模型，其中这些D。模拟畸变基因 产品可能会干扰精子中的染色质包装。最后，我们将研究 更广泛的进化意义，内源性siRNA如何可能解锁地图， 多个果蝇物种的基因组内冲突，并研究了一个基本原理， 类似哺乳动物减数分裂时的分子战斗。我们的多学科 研究将阐明组织特异性从头基因活性之间的联系机制 以及具有快速基因组动态的小RNA， 可能是物种形成的早期阶段。