Genetic Dissection of Wolbachia Infection in Drosophila Melanogaster

管体沃尔巴克氏体是已知分布最广泛的内共生微生物之一。它首先在库蚊中被发现，后来在超过20%的昆虫物种和大约25%的用于基因研究的黑腹果蝇中被发现。沃尔巴克氏菌擅长操纵宿主繁殖。在果蝇中，沃尔巴克氏菌主要引起细胞质不相容（CI），这是一种生殖隔离形式。CI的表达使受感染的雄性与未感染的雌性交配时无法生育后代。虽然受感染的雄性正常交配，转移精子和精子使卵子受精，但卵子无法完成核细胞增生而死亡。未感染的雄性和感染的雌性之间的反向杂交是可行的，但由于沃尔巴克氏体是通过雌性垂直传播的，因此所有产生的后代都被感染了。该研究项目将试图了解沃尔巴克氏体在黑腹果蝇睾丸分布的遗传基础及其对CI的影响。缺陷定位将确定对黑腹沼虾睾丸沃尔巴克氏体分布和密度有重大影响的位点。缺货库存将被检查是否存在沃尔巴克氏体。那些具有不同沃尔巴克氏体分布模式的菌株将进一步研究其引起CI的能力（或不能力）以及不同细菌分布的宿主遗传基础。在通过缺陷定位确定重要候选位点后，将研究不同外显率水平的等位基因对细菌分布和CI的影响。确定沃尔巴克氏体分布模式所涉及的基因和生化途径将促进对沃尔巴克氏体如何操纵果蝇宿主繁殖和精子发生的理解。它还可能提供线索，说明当沃尔巴克氏体感染更远亲的昆虫，特别是引起人类疾病的害虫（例如，由蚊子传播的疟疾）时，是什么途径被操纵的。这些知识也将有助于设计利用沃尔巴克氏体的有效虫害管理方案。

Wolbachia pipientis is one of the most widespread endosymbiotic microorganisms known. First characterized in mosquitoes of the Culex pipiens complex, it has since been found in greater than 20% of insect species and about 25% of Drosophila melanogaster used in genetic research. Wolbachia has specialized in the manipulation of host reproduction. In Drosophila, Wolbachia primarily causes cytoplasmic incompatability (CI), a form of reproductive isolation. The expression of CI renders infected males unable to father offspring when mated to uninfected females. While infected males mate normally, transfer sperm and the sperm fertilize the egg, the egg fails to complete karyogamy and dies. Reciprocal crosses between uninfected males and infected females are viable, but since Wolbachia are transmitted vertically through the female, all resulting progeny are infected. The research project will attempt to understand the genetic basis of Wolbachia distribution in Drosophila melanogaster testes and the resulting effects on CI. Deficiency mapping will identify loci with large effects on Wolbachia distribution and density within D. melanogaster testes. Deficiency stocks will be screened for the presence of Wolbachia. Those strains with dissimilar patterns of Wolbachia distribution will be studied further for their ability (or inability) to cause CI as well as the for the host genetic basis of differential bacterial distribution. Following identification of important candidate loci through deficiency mapping, alleles with different levels of penetrance will be studied for their impact on bacterial distribution and CI. The identification of genes and biochemical pathways involved in determining Wolbachia distribution patterns will advance the understanding of how Wolbachia manipulate host reproduction in Drosophila and spermatogenesis in general. It may also provide clues as to what pathways are manipulated when Wolbachia infect more distantly related insects, particularly insect pests that cause human diseases (for example, malarial diseases transmitted by mosquitoes. Such knowledge will also aid in the design of effective pest management programs utilizing Wolbachia.