The evolutionary genetics and genomics of Wolbachia effects on host physiology

沃尔巴克氏体对宿主生理学影响的进化遗传学和基因组学 项目简介：昆虫是地球上最丰富的生物群体，约 这些物种中有一半感染了母体传播的沃尔巴克氏体细菌。沃尔巴克氏体成为 被认为是操纵宿主繁殖的;例如，许多沃尔巴克氏体菌株引起细胞质 不相容性（CI），当沃尔巴克氏体感染的雄性与 未感染的女性几种感染果蝇的沃尔巴克氏体菌株也能阻断病毒， 渗入到埃及伊蚊中，自然感染D.黑腹果蝇作为生物控制 媒介传播疾病（特别是登革热和现在的寨卡病毒）。尽管沃尔巴克氏体生物防治取得了初步成功， 关于有利于沃尔巴克氏体感染的条件存在很大的知识缺口。例如，在没有 沃尔巴克氏体感染的宿主系统是了解沃尔巴克氏体感染如何积极影响宿主健身， 从低频传播。这是令人惊讶的考虑到沃尔巴克氏体已蔓延成为最 最普遍的共生体研究人员的长期目标是了解遗传和非生物 这种环境有利于沃尔巴克氏体感染的传播和持续。核心假设是， 宿主细胞核、宿主线粒体和沃尔巴克氏体基因组（以及环境）之间的相互作用 确定沃尔巴克氏体对宿主的适应性影响。基本原理是，利用自然发生的遗传 变化，结合综合方法和新技术，现在使这些差距， 知识要填满。在初步数据和成熟理论的指导下，拟议的研究将测试 通过确定基因组和环境相互作用对以下方面的贡献来确定中心假设：1）变异 在CI，细胞生理学和健身;和2）内沃尔巴克氏体细胞的丰度和分布的变化 宿主组织，这是有效的母体沃尔巴克氏体传播给宿主后代的基础。自然采样 实验室构建的遗传变异和基因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体 影响焦点性状的基因组变异。拟议的项目将使用沃尔巴克氏体显微注射， 基因渗入候选Wolbachia和宿主背景，其中一些具有精确的组合 细胞核和线粒体基因组。这种设计使得能够明确测试不同 从基因组到影响适应性的表型变异。关于上述第二点，最近的数据表明， wMel传播在苍蝇和蚊子背景中对温度高度敏感。拟议 项目将使用分析化学和共聚焦显微镜来了解这种易感性的细胞基础。 这项拟议中的研究意义重大，因为它将确定遗传和非生物环境， 沃尔巴克氏体传播。这项拟议中的研究是创新的，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理解沃尔巴克氏体在自然界中的持久性。

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.