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中文摘要
翻译
有性繁殖为交配对的基因类型之间的成对相互作用提供了充足的机会。充斥着男性和女性相互作用的过程的一个后果是,进化可能无法优化两性的功能,相反,会保持高度的变异。这似乎是影响果蝇精子竞争和其他生殖健康属性的因素的情况。被称为附腺蛋白(ACP)的精液蛋白似乎专门调节这些相互作用的各个方面,与与ACP相互作用的雌性分子一起,它们充当量化特定雄性和雌性相互作用的分子入口。我们的第一个具体目标是使用来自自然种群的基因分离来量化雄性和雌性在生殖适合性组成部分中的相互作用,重点放在那些可能由附腺蛋白以及它们与雌性相互作用的蛋白质过程所介导的作用上。使用来自果蝇遗传参考小组的品系(其基因组序列和基因表达数据已经可用),并在适当的情况下补充来自五个广泛地理区域的额外品系,我们将在20x20部分双列设计中研究品系和区域内以及品系和区域之间的雄性×雌性交互作用。双性交配雌性的父子关系成功率、繁殖力、繁殖力和雌性生殖能力都将得到系统的评分。这项研究将量化生殖适合性成分,以验证AIMS 2和AIMS 3的结果。第二个目标是通过测试一系列特征良好的野生雌性基因型中特定雄性ACP基因的RNAi敲除来剖析雄性与雌性的交互作用。相同生殖表型的比较将使用正常表达ACPs的雄性进行评分,或者被特定ACPs的RNAi击倒。我们将首先关注与精子储存和/或精子竞争的影响有关的ACPs。此外,我们将通过测试性肽和性肽受体的不同等位基因之间的相互作用,来检验一个特定的测试案例,在这个测试案例中,男性和女性伴侣都是已知的。将识别对每个击倒反应过度和反应迟钝的雌性品系,我们将把总的相互作用划分为每个ACP介导的组件。通过扩大我们对男性和女性生殖贡献者遗传变异的理解,我们将获得关于遗传变异如何以及为什么在自然界中保持的洞察力。此外,由于我们研究的基因变异涉及基本的生殖功能,我们的结果将扩大理解人类特发性不孕不育病例的基础,特别是那些无法确定导致不孕不育的性别特定原因的病例,因此可能反映出伴侣之间的基因不相容。
英文摘要
Sexual reproduction provides ample opportunity for pairwise interactions between the genotypes of mating pairs. One consequence of processes that are rife with male x female interactions is that evolution may fail to optimize functions for either sex, and instead there is retained a high level of variation. This appears to be the case for factors influencing sperm competition and other reproductive fitness attributes in Drosophila. The seminal proteins known as accessory gland proteins (Acps) appear to be specialized for mediating aspects of these interactions, and along with the female molecules that interact with Acps, they serve as a molecular entré to quantifying specific male x female interactions. Our first specific aim is to use genetic isolates from natural populations to quantify male x female interactions in components of reproductive fitness with a focus on those likely to be mediated by Accessory Gland Proteins and the proteins processes with which they interact in females. Using lines from the Drosophila Genetic Reference Panel (for which both genome sequence and gene expression data are already available), supplemented where appropriate with additional lines from five broad geographic regions, we will examine male x female interactions both within and between lines and regions in a 20 x 20 partial diallel design. Paternity success in doubly-mated females, fecundity, fertility, and female remating receptivity will all be systematically scored. This study will quantify reproductive fitness components for validation of the findings of Aims 2 and 3. The second aim is to dissect male x female interactions by testing RNAi knockdowns of specific male Acp genes across a range of well-characterized wild female genotypes. Comparison of the same reproductive phenotypes will be scored using males that express Acps normally, or are knocked down by RNAi for specific Acps. We will begin with a focus on Acps that have been associated with effects on sperm storage and/or sperm competition. In addition, we will examine a specific test case in which both the male and female partners are known, by testing for interactions among variant alleles in Sex Peptide and the Sex Peptide receptor. Female lines that are hyper- and hyporesponsive to each knockdown will be identified, and we will partition total interaction into components mediated by each Acp. By extending our understanding of the genetic variation in male and female contributors to reproduction, we will obtain insights into how and why genetic variation is maintained in nature. Moreover, since the genes whose variation we examine involve basic reproductive functions, our results will expand the foundation for understanding cases of idiopathic human infertility, specifically those in which no sex-specific cause for the infertility can be identified and may thus reflect genetic incompatibility between the partners.
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Improving the efficiency and control of CRISPR/Cas9 gene drive systems
  • 批准号:
    9387508
  • 项目类别:
  • 资助金额:
    $19.51万
  • 财政年份:
    2017
  • 负责人:
    ANDREW G CLARK
  • 依托单位:
Population Genetic Consequences of Recent Explosive Population Growth in Humans
  • 批准号:
    8613540
  • 项目类别:
  • 资助金额:
    $58.89万
  • 财政年份:
    2014
  • 负责人:
    ANDREW G CLARK
  • 依托单位:
Genetic Transmission of Componenets of the Human Gut Microbiome
  • 批准号:
    10248711
  • 项目类别:
  • 资助金额:
    $8.14万
  • 财政年份:
    2011
  • 负责人:
    ANDREW G CLARK
  • 依托单位:
海外基金