Sex separation through targeting of conserved female-specific lethal genes in disease vector mosquitoes

项目摘要 雌性蚊子与雄性蚊子在形态、生理和行为特征上不同，这些特征促进 致病病原体的传播。尽管大多数调节性二型性的基因 蚊子的发育尚未确定，这些基因可能是 蚊子控制。女性特有的发育基因的特征也可以解释遗传 雄性蚊子的生产和分类战略，这是阻碍全球执行 几种新出现的基于种群的蚊子控制策略，这些策略依赖于大量释放雄性蚊子。 导致性别特异性致死效应的基因座簇被认为位于决定性别的M/m内 登革热媒介蚊子埃及伊蚊的基因座区域，但这些基因的同源性尚不清楚 之前已知的。最近一次高通量RNAi介导的筛查发现了雌性特异的幼虫致死 埃及斑潜蝇性别决定基因区的基因，包括几个已知与其他基因同源的基因 病媒蚊子的种类。针对这些基因的酵母干扰RNA杀幼虫剂杀死雌性A. 埃及伊蚊幼虫在发育过程中，但不影响雄性蚊子。拟议的研究计划将 验证有初步数据支持的假设，即这些基因的同源基因也具有 白纹伊蚊(多种虫媒病毒载体)冈比亚按蚊的雌性特异性幼虫致死位点 和致倦库蚊(西尼罗河和淋巴丝虫病媒介)。《公约》的具体目标 拟议的研究包括：i)RNAi介导的筛选预期的女性特有的致死基因 疾病媒介蚊子，II)构建和下选择针对蚊子的雌性特异性酵母幼虫 每个物种的基因，以及iii)开发基于酵母杀幼虫剂的大规模饲养Fit，交配- 所有三个物种的竞争雄蚊。预计这些研究将产生新的 针对雌性的幼虫控制策略，为蚊子性染色体的进化提供了洞察力 和性别指定机制，并阐明大规模饲养雄性的方法，这将有助于 在多种人类疾病媒介蚊子中新出现的基于种群的控制策略。

Project Summary Female mosquitoes differ from males in morphological, physiological, and behavioral traits that promote the spread of disease-causing pathogens. Although the majority of genes that regulate sexually dimorphic development in mosquitoes have not yet been identified, these genes may represent novel targets for mosquito control. Characterization of female-specific developmental genes could also elucidate genetic strategies for production and sorting of male mosquitoes, an obstacle that hinders global implementation of several emerging population-based mosquito control strategies that are dependent on mass releases of males. Clusters of loci that cause sex-specific lethal effects are believed to reside within the sex-determining M/m locus region of the dengue vector mosquito Aedes aegypti, but the identities of these genes were not previously known. A recent high-throughput RNAi-mediated screen uncovered female-specific larval lethal genes in the A. aegypti sex-determining locus region, including several genes with known orthologs in other species of disease vector mosquitoes. Yeast interfering RNA larvicides that target these genes kill female A. aegypti larvae during development, but do not impact male mosquitoes. The proposed research program will test the hypothesis, which is supported by preliminary data, that orthologs of these genes also function as female-specific larval lethal loci in Aedes albopictus (vector of multiple arboviruses), Anopheles gambiae (malaria vector), and Culex quinquefasciatus (West Nile and lymphatic filariasis vector). Specific aims of the proposed investigation include i) RNAi-mediated screening of prospective female-specific lethal genes in these disease vector mosquitoes, ii) construction and down-selection of female-specific yeast larvicides to target the genes in each species, and iii) development of protocols for yeast larvicide-based mass rearing of fit, mating- competitive male mosquitoes of all three species. It is anticipated that these studies will generate novel female-specific larvicidal control strategies, provide insight into the evolution of mosquito sex chromosomes and sex-specification mechanisms, and elucidate methodology for mass rearing of males that will facilitate emerging population-based control strategies in multiple species of human disease vector mosquitoes.