Identification of Genes that Cause Sterility in Male Malaria Mosquitoes

描述(申请人提供)：在过去十年中，撒哈拉以南非洲的疟疾死亡人数下降了近40%，这主要是由于针对按蚊媒介的杀虫剂的使用增加了。然而，蚊子种群的生理和行为抗性威胁着当前控制努力的可持续性。为了利用这个机会 在过去十年取得成功的基础上，需要将新的控制技术与更明智地使用杀虫剂结合起来。不育昆虫技术涉及大规模饲养雄性蚊子，然后通过辐射对雄性蚊子进行消毒，并将其释放到野外与雌性蚊子交配。虽然在概念上很简单，并成功地应用于其他昆虫，但不育昆虫技术在非洲按蚊上并不奏效，主要是因为辐射降低了雄性蚊子的整体适应能力，使它们成为相对于野生型雄性蚊子的较差竞争对手。我们的提议旨在使用尖端的组合基因组学方法来识别对男性生育能力至关重要的基因，为创造不育但其他正常的雄性蚊子奠定基础。非洲大多数重要的疟疾媒介属于冈比亚按蚊复合体，该复合体由至少8个形态相同但在遗传、行为和生态上截然不同的物种组成。而非洲热带媒介的多样性 系统通常被认为是疟疾控制的障碍，我们计划将其用于我们的优势：经典研究表明，当两个物种在AN内。冈比亚复合体正反交，F_1代雄性完全不育。然而，F1杂交雌性是完全可育的，可以回交产生从完全不育到完全可育的重组雄性后代，这为将基因型与表型联系起来提供了基础。在接下来的资助中，我们计划剖析两个载体物种之间杂交雄性不育的遗传基础。冈比亚亚纲和An.梅鲁斯。通过将高通量定量基因组学与有针对性的转录和公开的群体遗传数据相结合，我们的方法将产生一份候选不育基因的精选清单。最终，我们的项目旨在 利用非洲媒介系统的复杂性来对付自己；识别对精子正常发育至关重要的基因，将使通过抑制种群来控制媒介的新战略成为可能。

DESCRIPTION (provided by applicant): Over the past decade, malaria deaths in Sub-Saharan Africa decreased nearly 40% primarily due to increased use of insecticides that target the Anopheles mosquito vector. However, both physiological and behavioral resistance in the mosquito population threatens the sustainability of current control efforts. In order to capitalize upon the success of the past decade, novel control techniques need to be integrated with more judicious use of insecticides. The sterile insect technique involves mass-rearing of male mosquitoes, which are then sterilized via irradiation and released into the wild to mate with females. While conceptually simple and successfully deployed in other insects, the sterile insect technique has not worked on African Anopheles primarily because irradiation reduces the overall fitness of males, making them poor competitors relative to wild type males. Our proposal aims to use a cutting-edge, combinatorial genomics approach to identify genes that are critical to male fertility, laying the foundation for creating male mosquitoes that are sterile, but otherwie normal. A majority of the important malaria vectors in Africa belong to the Anopheles gambiae complex, which consists of at least eight morphologically identical -- but genetically, behaviorally, and ecological distinct -- species. While the diversity of the Afrotropical vectorial system is normally regarded as an impediment to malaria control, we plan to use it to our advantage: classical studies showed that when two species within the An. gambiae complex are reciprocally crossed the F1 hybrid males are completely sterile. However, F1 hybrid females are fully fertile and can be backcrossed to generate recombinant male progeny that range from completely sterile to fully fertile, providing the foundation to connect genotype with phenotype. I the following grant, we plan to dissect the genetic basis of hybrid male sterility between the two vector species An. gambiae and An. merus. By combining high-throughput quantitative genomics with targeted trasncriptomics and publically-available population genetic data our approach will result in a select list of candidate sterility genes. Ultimately, our project aims to use the complexity of the African vectorial system against itself; identification of genes criticalto proper sperm development will enable new strategies for vector control through population suppression.