Characterization & Organization of Transposable Elements

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DESCRIPTION (provided by the applicant): The Anopheles gambiae species complex includes An: garnbiae sensu stricto, the most important vector of malaria, a disease that causes more than a million deaths every year. Effective malaria control requires multi-front efforts including a better understanding of its vectors. Our long-term goals are to 1) understand the diversity, abundance, stability, population dynamics, evolution, and impacts of transposable elements (TEs) in An. gambiae and 2) develop population genomic approaches based on interspersed TEs to study the genetic heterogeneity of An. gambiae s.s. populations. We propose a collaborative effort to explore the anticipated An. gambiae genome sequence with an interdisciplinary team that have demonstrated expertise in genomic, bioinformatic, molecular, and evolutionary analysis of mosquito TEs, and in population genetics of An. gambiae s. s. and its species complex. We will focus on DNA transposons and miniature inverted-repeats TEs (MITEs), which share essential structures and probably similar transposition mechanisms. We will pursue the following Specific Aims: 1) Make the first-round examination of the diversity, abundance, and molecular characteristics of TEs in An. gambiae. s.s. 2) Study the evolutionary history and mode of amplification of MITEs and DNA transposons in An. gambiae. s.s. and its sibling species. 3) Examine the impacts of MITEs and DNA transposons on An. gambiae. s.s. genome structure and evolution. 4) Determine copy number variation and insertion site polymorphism of MITEs and DNA transposons in wild populations of An. gambiae. s.s. 5) Develop novel population genomic tools for An. gambiae s.s.,using insertion polymorphism markers derived from both DNA and RNA-mediated TEs. This work will contribute, at three different levels, to the improvement of vector control and surveillance and the development of alternative malaria control strategies, both of which are urgently needed. First, powerful population genomic tools will be provided to study genetic heterogeneity in An. gambiae s. s. populations, which can affect disease transmission and the efficiency of control measures. Second, the proposed work will yield new insights into endogenous TEs in An. gambiae, which will contribute to the strategy to control mosquito-borne diseases by TE-based genetic modifications. Finally, this work will enhance our understanding of the basic genetics of An. gambiae by systematically investigating TEs, which are substantial and potentially potent components of the genome.