The evolutionary genetics and genomics of Wolbachia effects on host physiology

项目：沃尔巴克氏菌的进化遗传学和基因组学对宿主生理的影响 项目摘要：昆虫是地球上最丰富的有机体，大约 这些物种中有一半感染了通过母体传播的沃尔巴克氏菌。沃尔巴克氏菌变成了 被公认为操纵宿主繁殖；例如，许多沃尔巴克氏菌株能引起细胞质 不相容(CI)，当感染沃尔巴克氏菌的雄性与 未受感染的雌性。几种感染果蝇的沃尔巴克氏菌株也能阻止病毒，而且当 导入埃及伊蚊的wmel菌株自然感染黑纹伊蚊作为生防菌 媒介传播疾病(特别是登革热和现在的寨卡病毒)。尽管沃尔巴克氏菌生物防治取得了初步成功， 关于有利于沃尔巴克氏菌感染的条件，知识存在很大差距。例如，在no中 沃尔巴克氏菌感染的宿主系统了解沃尔巴克氏菌感染如何积极影响宿主适应 从低频率传播。考虑到沃尔巴克氏菌已经蔓延到世界上 地球上普遍存在的共生体。研究人员的长期目标是了解基因和非生物 有利于沃尔巴克氏菌感染传播和持续的环境。中心假设是 宿主核、宿主线粒体和沃尔巴克氏菌基因组(以及环境)之间的相互作用 确定沃尔巴克氏菌对寄主的适合性影响。其基本原理是利用自然产生的基因 变化，再加上综合方法和新技术，现在使这些差距成为可能 知识有待充实。在初步数据和成熟理论的指导下，拟议的研究将检验 通过确定基因组和环境相互作用对：1)变异的贡献来确定中心假说 在CI中，细胞生理学和适合性；以及2)沃尔巴克氏菌细胞的丰度和分布在 宿主组织，这是有效的母体沃尔巴克氏菌传播给宿主后代的基础。自然采样 在实验室构建的遗传变异和基因类型将与下一代测序一起使用 回答问题。例如，初步分析已经确定了宿主背景和沃尔巴克氏菌 影响局部性状的基因组变异。拟议的项目将使用沃尔巴克氏菌微量注射来 相互引入候选人沃尔巴克氏菌和宿主背景，其中一些有精确的组合 核基因组和线粒体基因组。此设计允许显式测试不同的 基因组对影响适合度的表型变异的影响。关于上述第二点，最近的数据表明 在苍蝇和蚊子背景下，wMel传播都非常容易受到温度的影响。建议数 项目将使用分析化学和共聚焦显微镜来了解这种敏感性的细胞基础。 这项拟议的研究意义重大，因为它将确定促进 沃尔巴克氏菌蔓延。这项拟议的研究具有创新性，因为它弥合了基因组研究之间的差距， 细胞和自然遗传变异；这些差距目前阻碍了对沃尔巴克氏菌在自然界中持久性的理解。

Project: The evolutionary genetics and genomics of Wolbachia effects on host physiology Project Summary: Insects are the most abundant group of organisms on the planet, and the cells of about half of these species are infected with maternally transmitted Wolbachia bacteria. Wolbachia became recognized for manipulating host reproduction; for example, many Wolbachia strains cause cytoplasmic incompatibility (CI), which generates increased embryo mortality when Wolbachia-infected males mate with uninfected females. Several Wolbachia strains that infect Drosophila flies also block viruses, and when introgressed into Aedes aegypti, the wMel strain that naturally infects D. melanogaster serves as a biocontrol of vector-borne disease (particularly dengue and now Zika). Despite the initial success of Wolbachia biocontrol, large gaps in knowledge exist regarding the conditions that favor Wolbachia infections. For example, in no Wolbachia-infected host system is it understood how Wolbachia infections positively affect host fitness to spread from low frequencies. This is surprising considering that Wolbachia have spread to become the most prevalent symbiont on the planet. The investigator's long-term goal is to understand the genetic and abiotic contexts that favor the spread and persistence of Wolbachia infections. The central hypothesis is that interactions among host nuclear, host mitochondrial, and Wolbachia genomes (and the environment) determine the fitness effects of Wolbachia on hosts. The rationale is that leveraging naturally occurring genetic variation, in combination with integrative approaches and new technology, now enables these gaps in knowledge to be filled. Guided by preliminary data and well-established theory, the proposed research will test the central hypothesis by determining contributions of genomic and environmental interactions to: 1) variation in CI, cell physiology, and fitness; and 2) variation in the abundance and distribution of Wolbachia cells within host tissues, which underlies efficient maternal Wolbachia transmission to host offspring. Naturally sampled genetic variation and genotypes constructed in the lab will be used alongside next-generation sequencing to answer questions. For example, preliminary analyses have identified both host backgrounds and Wolbachia genomic variants that influence the focal traits. The proposed projects will use Wolbachia microinjections to reciprocally introgress candidate Wolbachia and host backgrounds, some of which have precise combinations of nuclear and mitochondrial genomes. This design enables an explicit test for contributions of different genomes to variation in phenotypes that affect fitness. Regarding point two above, recent data indicate that wMel transmission is highly susceptible to temperature in both fly and mosquito backgrounds. The proposed projects will use analytical chemistry and confocal microscopy to understand the cell basis of this susceptibility. The proposed research is significant because it will identify the genetic and abiotic contexts that facilitate Wolbachia spread. The proposed research is innovative because it bridges gaps between studies of genomes, cells, and natural genetic variation; these gaps currently inhibit understanding Wolbachia persistence in nature.