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

基本信息

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
项目类别：
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

项目摘要

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元素加剧了基因组内的冲突，它们本质上出现在基因组中。如果不加以控制，这些后果可能是灾难性的个人和/或人群。因此，此类冲突会产生强大的压力创新对抗镇压机制。这明显地体现在悖论中减数分裂驱动系统，其中自私基因的野生型活动可以具有造成后代性别比例偏差的有害后果（通常消除雄性），或诱导明显的不育。然而，人们对分子的了解却相对较少。减数分裂驱动基因的机制及其控制。我们最近的工作首先提供了有证据表明，最近进化的性别偏见和不育诱导系统非模型果蝇 D. simulans 受到内源 siRNA 位点的抑制。这提供了为研究转录后如何驯服减数分裂驱动基因座奠定了独特的基础等级。尽管人们对自私减数分裂的生化功能知之甚少驱动基因座，我们的数据支持可测试的模型，其中这些 D. simulans 扭曲基因产品可能会干扰精子中的染色质堆积。最后，我们将检查内源性 siRNA 如何解锁基因图谱的更广泛的进化意义多个果蝇物种的基因组冲突，并检查其基本原理哺乳动物减数分裂过程中类似的分子战争。我们的多学科研究将阐明连接组织特异性从头基因活性的机制以及具有快速基因组动态的小RNA，可能会造成生殖隔离个体，可能是物种形成道路上的早期步骤。