Drosophila Genes Causing Male X Female Interactions in Reproduction

果蝇基因导致雄性 X 雌性在繁殖中相互作用

• 批准号: 8907790
• 负责人: ANDREW G CLARK
• 金额: $ 33.44万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-24 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8907790
• 关键词: Affect; American; Animal Model; Behavioral; Biomedical Research; Candidate Disease Gene; Collection; Communities; Complex; Couples; Data; Drosophila genus; Drosophila melanogaster; Evolution; Female; Fertility; Fertilization; Foundations; GRP gene; Gene Expression; Gene Expression Profile; Genes; Genetic; Genotype; Goals; Human; Image; Inbreeding; Individual; Infertility; Label; Learning; Mediating; Modeling; Molecular; Nature; Nervous System Physiology; Neurologic; Neurons; Outcome; Partner in relationship; Phenotype; Physiological; Play; Process; Proteins; RNA Interference; RNA Sequences; Relative (related person); Reproduction; Research; Resistance; Role; Seminal; Series; System; Testing; Variant; Whole Organism; Women' s Role; Work; base; differential expression; egg; gene discovery; genome sequencing; interest; knock-down; male; mutant; phenomenological models; reproductive; reproductive function; research study; response; sex; sperm cell; success; transcriptome sequencing; zygote

DESCRIPTION (provided by applicant): The determinants of which particular combinations of sperm and egg are successful in forming a zygote involve a myriad of molecular, cellular, neurological and whole-organism behavioral attributes. Our past work has focused on the phenomenology of differential success of the sperm in multiply mated female Drosophila, and screens for genes that impact this sperm competition have illuminated many aspects of the process. The first aim of our continuing effort is to determine the role(s) in sperm success of genes expressed by the female in her reproductive tract. To dissect the functional role of these genes in sperm use, we will apply highly targeted RNAi knockdown and assess the impact of loss of expression of these genes in the female reproductive tract. This is readily accomplished with the UAS-GAL4 system, using GAL4 drivers that express in the female reproductive tract. Judicious criteria will be applied to select candidates for knockdown and we are especially interested in the set of genes expressed in females that have neurological function. Knockdowns of female response genes will be tested in a battery of sperm competition tests against a set of 16 inbred sequence-known males and seminal protein nulls to try to quantify male x female interaction as well as testing specific interactions. Our second aim is to quantify genetic differences among males in their ability to influence post-mating transcriptome responses in females, and the roles of those expression changes on sperm competition. Females will be mated with males drawn from the Drosophila Genetic Reference Panel (for which both genome sequence and gene expression data are already available) and reproductive tracts will be dissected and subjected to RNA-sequencing. Analysis will provide a detailed picture of which genes respond transcriptionally to mating, and which genes respond differentially to different male genotypes. These genes will in turn be knocked down in females to see if they play a role in sperm competition. Because 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.

描述（由申请人提供）：精子和卵的特定组合在形成合子方面的决定因素涉及无数的分子，细胞，神经系统，神经系统和全生物行为属性。我们过去的工作集中于精子在倍增的雌性果蝇中的差异成功的现象学上，以及影响这种精子竞争的基因的筛选，阐明了该过程的许多方面。我们持续努力的第一个目的是确定雌性在生殖道中表达的基因成功中的作用。为了剖析这些基因在精子使用中的功能作用，我们将应用高度靶向的RNAi敲低，并评估这些基因在女性生殖道中表达的丧失的影响。这很容易使用UAS-GAL4系统，使用女性生殖道中表达的GAL4驱动器来完成。明智的标准将应用于选择敲低的候选者，我们对在具有神经功能的女性中表达的基因特别感兴趣。雌性反应基因的敲低将在一系列精子竞争测试中进行测试，以相对于16个近交序列的雄性和精液蛋白质无效，以试图量化男性X雌性相互作用以及测试特定的相互作用。我们的第二个目的是量化男性在影响女性中交配后转录组反应的能力以及这些表达在精子竞争中的作用的作用。女性将与从果蝇遗传参考面板中得出的雄性（基因组序列和基因表达数据都可以使用），并将剖析生殖道并进行RNA序列。分析将提供哪些基因对交配的转录反应，以及哪些基因对不同的男性基因型的反应。这些基因反过来将在女性中被击倒，以查看它们是否在精子竞争中发挥作用。由于我们研究的变异的基因涉及基本的生殖功能，因此我们的结果将扩大理解特发性人类不孕症病例的基础，特别是那些无法识别出不育性的性别原因的基因，因此可以反映伴侣之间的基因不兼容。