Male x Female Protein Interactions Mediating Reproductive Success in the Drosophila Mating Plug

雄性与雌性蛋白质相互作用介导果蝇交配插头的繁殖成功

• 批准号: 10824541
• 负责人: Jolie Anna Carlisle
• 金额: $ 6.91万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10824541
• 关键词: Affect; Automobile Driving; Behavior; Behavioral; Biological Models; Candidate Disease Gene; Coagulation Process; Complex; Conflict (Psychology); Copulation; Deposition; Drosophila genus; Ejaculation; Ensure; Evolution; Female; Fertilizers; Gene Expression; Genes; Genetic; Genetic Variation; Genomics; Human; Infertility; Invertebrates; Libido; Mammals; Mediating; Molecular; Molecular Evolution; Multiple Partners; Nervous System; Neurons; Outcome; Ovulation; Partner in relationship; Phenotype; Physiology; Population; Production; Proteins; RNA Interference; Regulation; Reproduction; Reproductive Process; Seminal fluid; Shapes; Time; Tissues; Uterus; Variant; cell type; egg; fighting; fly; genetic resource; genome resource; genome wide association study; knock-down; male; neural; neuromuscular; neuroregulation; offspring; paralogous gene; pressure; reproductive; reproductive function; reproductive outcome; reproductive success; reproductive tract; response; sex; sperm cell; undergraduate student; Affect; Automobile Driving; Behavior; Behavioral; Biological Models; Candidate Disease Gene; Coagulation Process; Complex; Conflict (Psychology); Copulation; Deposition; Drosophila genus; Ejaculation; Ensure; Evolution; Female; Fertilizers; Gene Expression; Genes; Genetic; Genetic Variation; Genomics; Human; Infertility; Invertebrates; Libido; Mammals; Mediating; Molecular; Molecular Evolution; Multiple Partners; Nervous System; Neurons; Outcome; Ovulation; Partner in relationship; Phenotype; Physiology; Population; Production; Proteins; RNA Interference; Regulation; Reproduction; Reproductive Process; Seminal fluid; Shapes; Time; Tissues; Uterus; Variant; cell type; egg; fighting; fly; genetic resource; genome resource; genome wide association study; knock-down; male; neural; neuromuscular; neuroregulation; offspring; paralogous gene; pressure; reproductive; reproductive function; reproductive outcome; reproductive success; reproductive tract; response; sex; sperm cell; undergraduate student

PROJECT SUMMARY In both mammals and invertebrates, initiation of post-mating responses in the female post-copulation is known to contribute to reproductive success. Seminal fluid proteins (Sfps) have been shown to initiate many of these responses. However, male x female interactions are underexplored as contributors to infertility. Investigating the mechanisms and evolution of male x female interactions is critical for understanding the complexities of reproduction. I will use D. melanogaster as a model system for investigating post-copulatory male x female interactions via characterization of male and female contributions to the Drosophila mating plug’s (MP) formation and ejection. In Drosophila, the MP forms in the uterus of the female via coagulation of male- ejaculated Sfps and some female reproductive tract proteins. Genetic disruption of the MP impacts reproductive outcomes by affecting sperm retention; however, little is known about the male and female proteins (and their interactions) that modulate mating plug ejection (MPE) rates either directly by contributing to MP composition/degradation or indirectly by regulating female ejection behavior. In Aims 1 & 2 I will respectively use female or male phenotypic variation in the Drosophila Genomic Reference Panel to perform a GWAS on MPE timing. I will then functionally investigate how top gene candidates mediate MPE timing. I have concluded a GWAS on female MPE timing and have so far identified 4 neuronal genes that regulate female MPE (Aim 1). Using highly tissue- and cell type- specific knockdown of gene candidate expression via RNA interference, I will more deeply characterize neuronal regulation of female MPE timing. After also identifying and characterizing male genes regulating MPE timing (Aim2) I will perform a 6x6 grid cross of males and females with disrupted function of MPE genes to investigate the presence of complex non-additive male x female MPE interactions. Finally, I will investigate the molecular evolution and function of male and female genes contributing to MP composition (Aim 3). I discovered that many male and female MP genes are closely paralogous to each other and evolving under positive selection, potentially suggestive of evolution under sexual conflict. After fully characterizing the evolution and coevolution of these male and female MP paralogs, I will investigate their sex-specific functions in MPE and MP formation. Observation of opposing functions for paralogous male and female MP genes would point to sexual conflict driven evolution caused by opposing sex-specific optimal mating strategies. Observation of complementary functions would indicate similar evolutionary pressures acting on male and female paralogs to cooperatively ensure optimal reproductive outcomes.

项目摘要 在哺乳动物和无脊椎动物中，已知女性人口后的交配反应的倡议已知 为生殖成功做出贡献。已经显示出精液蛋白（SFP）启动其中许多 回答。然而，男性X女性相互作用被视为不育的贡献者。调查 男性X女性相互作用的机制和演变对于理解复杂性至关重要 生殖。我将使用D. melanogaster作为模型系统，用于研究吞噬后男性X​​女性 通过表征男性和女性对果蝇交配塞（MP）的贡献的相互作用 形成和弹出。在果蝇中，MP在女性的子宫中形成，是通过男性的凝结而形成的 射精的SFP和一些女性生殖道蛋白。 MP影响的遗传破坏 通过影响精子保留来生殖结果；但是，对男性和女性知之甚少 通过有助于 MP组成/降解或间接调节女性射血行为。在目标1和2中我会 在果蝇基因组参考面板中分别使用雌性或男性表型变异 在MPE时机上执行GWAS。然后，我将在功能上研究顶级基因候选者如何介导MPE 定时。我已经在女性MPE时机上得出了一个GWA，到目前为止，我已经确定了4个神经元基因 调节女性MPE（AIM 1）。使用高度组织和细胞类型 - 候选基因的特异性敲低 通过RNA干扰的表达，我将更深入地表征女性MPE时间的神经元调节。 在识别和表征调节MPE时序的男性基因之后（AIM2），我将执行6x6网格 男性和女性的交叉具有破坏MPE基因功能的杂交 复杂的非加节雄性X雌性MPE相互作用。最后，我将研究分子进化和 有助于MP组成的男性和女性基因的功能（AIM 3）。我发现很多男性 雌性MP基因彼此紧密相吻合，并在阳性选择下发展， 可能暗示性冲突下的进化。在充分表征演变之后 这些男性和女性MP旁系同源物的共同进化，我将研究其在MPE中的性别特定功能 和MP组。观察寄生的男性和女性MP基因的相反功能会指出 性冲突驱动力的演变是由针对性别的最佳交配策略引起的。观察 完全的功能将表明作用于男性和女性旁系同源的类似的进化压力 合作确保最佳复制结果。