Genomic analysis of mating and sexual conflict in Caenorhabditis

描述(申请人提供)：通过有性繁殖进行的基因交换的不同模式可以对种群内和种群间的遗传变异和进化差异产生深远影响。当交换的频率可以在几个数量级上变化时，这一点尤其正确。利用雄雄异株模式线虫--秀丽线虫及其雌雄同源的近缘线虫--雷曼线虫，提出了平行的研究项目，以识别或分类菌株之间差异繁殖的基因和这些生物性别之间的差异适合度。本研究的目的是：1.定位导致不同品系男性频率差异的基因，并对其功能进行评估。初步数据显示，在线虫中维持的雄性频率可能会在不同品系之间存在高达3000倍的差异。利用240个重组自交系(RIL)在&gt；1200单核苷酸多态基因座上进行基因分型，将利用高通量方法(包括基因表达分析、干扰RNA敲除(RNAi)和转化挽救)来识别和评估与雄性交配能力差异相关的基因组区域。2.确定导致性冲突和精子竞争的基因的性质，这是线虫属的一个严格异交物种，正在成为进化生态学研究的模式生物。初步结果表明，该物种内存在精子竞争和性冲突。根据雌性和雄性的遗传背景，雄性交配可能会以特定品系的方式减少雌性寿命高达33%。由于雄性对雌性寿命和精子竞争能力的影响而产生差异的品系间的杂交将被用来鉴定这些雄性交配能力相关性状的遗传基础。 相关性：理解复杂性状的遗传基础，包括已知受大量相互作用的基因影响的人类疾病，如心脏病、肥胖症和精神疾病，是现代生物学的主要挑战之一。这项工作是一个如何利用高通量基因组方法来理解复杂性状的分子遗传基础的模型。此外，性别特有的效应和相互作用是包括人类在内的所有有机体的普遍特征，了解它们的遗传基础可以洞察构成基因组很大一部分的力量。

DESCRIPTION (provided by applicant): Differential patterns of genetic exchange via sexual reproduction can have a profound impact on genetic variation and evolutionary divergence within and between populations. This is especially true when the frequency of exchange can vary over several orders of magnitude. Using the androdioecious model nematode, C. elegans, and its dioeceous relative, C. remanei, parallel research projects are proposed to identify or classify the genes underlying differential reproduction among strains and differential fitness between sexes of these organisms. The objectives of this research are to: 1. Map the genes contributing to among strain differences in male frequency and evaluate their function. Preliminary data demonstrates that the frequency of males maintained in C. elegans can differ between strains by as much as factor of 3,000. Using 240 recombinant inbred lines (RIL) that have been genotyped at >1200 single nucleotide polymorphic loci, genomic regions associated with this difference in male mating ability will be identified and functionally assessed using high throughput approaches including the analysis of gene expression, knockdown using interfering RNA (RNAi), and transformation rescue. 2. Determine the nature of the genes underlying sexual conflict and sperm competition in C. remanei, a strictly outcrossing species of Caenorhabditis that is emerging as a model organism for evolutionary ecology research. Preliminary results indicate the presence of sperm competition and sexual conflict within this species. Depending on female and male genetic backgrounds, male mating can reduce female longevity by as much as 33% in a strain specific manner. Crosses among strains divergent for male effects on female longevity and sperm competitive ability will be used to identify the genetic basis of these male mating ability associated traits. Relevance: Understanding the genetic basis of complex traits, including human conditions such as heart disease, obesity, and mental illness known to be influenced by a large number of interacting genes, is one of the major challenges of modern biology. This work serves as a model of how one can utilize high-throughput genomic approaches to understand the molecular genetic basis of complex traits. Further, sex specific effects and interactions are ubiquitous features of all organisms, including humans, and understanding their genetic basis can yield insights into the forces structuring what is certain to be a large fraction of the genome.