Comparative Genomics of Anopheline Mosquitoes

描述(申请人提供)：按蚊是疟疾的主要传播媒介。蚊子研究的最新进展，特别是非洲冈比亚按蚊主要媒介基因组序列草案的公布，为我们提供了令人兴奋的机会，极大地提高了我们对蚊子遗传学、行为和生理学的理解。蚊子生物学方面的新见解无疑将有助于制定防治疟疾和其他蚊媒疾病的新战略。这一建议的基本概念是将比较研究与现代基因组技术相结合，以帮助实现AN的承诺。冈比亚亚科基因组计划。这个探索性的R21项目的长期目标是开发一种对目标基因组区域进行多物种比较的有效方法，以阐明是什么使蚊子成为病原体的合格媒介、嗜人的叮咬者以及在不同生态条件下的适应性幸存者。在这里，我们将针对包含气味受体(GPRor)基因或基因簇的基因组区域，因为它们在蚊子寻找宿主的行为中具有潜在的作用。冈比亚亚目。我们将追求三个具体目标：1)从An中随机挑选12个BAC克隆。Stephensi获得关于An之间相对基因组组织和进化分歧的基线信息。Stephensi和An.冈比亚亚目。2)针对包含GPRor基因或基因簇的6个区域进行配对比较。Stephensi和An.冈比亚研究进化差异、保守的调控元件以及这些基因的扩展/丢失/重排。3)进一步针对2个GPRor区域进行多物种比较，以有效地确定潜在的调控元件，检测局部基因扩展/丢失/重排，并检查这些遗传变化与生物适应之间的可能相关性。

DESCRIPTION (provided by applicant): Anopheline mosquitoes constitute the primary vectors of malaria. Recent developments in mosquito research, that were highlighted by the publication of a draft genome sequence of the primary African malaria vector Anopheles gambiae, provide exciting opportunities to greatly enhance our understanding of mosquito genetics, behavior, and physiology. New insights in mosquito biology will undoubtedly facilitate the development of novel strategies to combat malaria and other mosquito-borne diseases. The basic concept underlying this proposal is to combine comparative inquiry with modern genomic technology to help realize the promise of the An. gambiae genome project. The long-term objective of this exploratory R21 project is to develop an efficient method of multi-species comparisons of targeted genomic regions to illuminate what makes a mosquito a competent vector for pathogens, an anthropophilic biter, and an adaptive survivor under different ecological conditions. Here we will target genomic regions that contain odorant receptor (GPRor) genes or gene clusters because of their potential roles in host-seeking behavior of An. gambiae. We will pursue three Specific Aims: 1) Sequence 12 randomly picked BAC clones from An. stephensi to obtain baseline information on the relative genomic organization and evolutionary divergence between An. stephensi and An. gambiae. 2) Target 6 regions that contain GPRor genes or gene clusters for pair-wise comparisons between An. stephensi and An. gambiae to examine the evolutionary divergence, conserved regulatory elements, and expansions/loss/rearrangements of these genes. 3) Further target 2 GPRor regions for multi-species comparisons to efficiently identify potential regulatory elements, detect local gene expansions/loss/rearrangements, and examine possible correlations between these genetic changes and biological adaptations.