Evolution of interactions between Wolbachia and its hosts: Drosophila model syste

描述(由申请人提供)： 项目：沃尔巴克氏菌与其宿主之间相互作用的进化：果蝇模型系统。项目摘要：沃尔巴克氏菌是生活在无脊椎动物宿主细胞内的细菌。它们通常通过母体传播，并经常通过操纵宿主繁殖在人群中传播。他们最常见的生殖操作是“细胞质不相容”(CI)，即当受感染的雄性与未受感染的雌性交配时，会增加胚胎死亡率。CI使沃尔巴克氏菌进入蚊子种群，并被用来将抑制致病病毒(特别是登革热)的沃尔巴克氏菌菌株引入自然蚊子种群。沃尔巴克氏杆菌具有阻断病原体传播的能力，因此有望控制许多通过昆虫在人与人之间传播的疾病，包括疟疾和西尼罗河病毒。由于沃尔巴克氏菌是母系遗传的，它们的进化是为了帮助宿主生存和繁殖，例如，通过抑制病原体和增加宿主的繁殖力。相反，因为沃尔巴克氏菌的繁殖操作会杀死胚胎，宿主可能会进化来抑制这些有害的影响(而不会损害有益的影响)。沃尔巴克氏菌的健康应用依赖于了解它们在自然界中的传播以及沃尔巴克氏菌与宿主快速共同进化的潜力。自然界中沃尔巴克氏菌与宿主相互作用的知识仅限于少数几个模型系统。果蝇的沃尔巴克氏菌感染为理解沃尔巴克氏菌的快速空间传播、共同进化变化以及这些现象背后的分子机制提供了范例。对沃尔巴克氏杆菌感染最了解的两种是拟态杜氏菌(特别是WRI)和黑腹杜氏菌(WMel)。这些感染在自然界中以根本不同的机制持续存在，只有WRI-Simans才能完全解释。然而，wMel-Blackogaster协会的历史显然要悠久得多。本项目旨在通过(1)扩展WRI-Simans和wMel-Blackogaster的现场和实验室分析，以及(2)描述Wolbchia与宿主的相互作用和共同进化，通过至少30个感染Wolbachia的果蝇物种来加深对Wolbachia种群动态和进化的深入了解。基因组学、细胞生物学和进化遗传学的工具已经针对果蝇进行了优化，将被用于研究自然界中的种群和进化动力学。例如，微注射技术将在果蝇物种之间移动沃尔巴克氏菌，并将沃尔巴克氏菌从宿主影响中解脱出来。在过去的20年里，WRI和wMel在澳大利亚蔓延，WRI在加利福尼亚州发展。这些当前事件提供了一个独特的机会，可以在行动中跟踪人口和进化动态。将对另外30多种已知携带沃尔巴克氏菌的果蝇进行详细研究，以更全面地了解沃尔巴克氏菌与宿主之间的共同进化轨迹、时间尺度和机制。这项拟议的研究基于实地调查、田间和实验室实验、比较基因组学和表型效应的实验室分析相结合的基础，将为了解沃尔巴克氏菌在其他系统中可能的轨迹提供基础，包括应用于蚊子传播疾病的媒介。

DESCRIPTION (provided by applicant): Project: Evolution of interactions between Wolbachia and its hosts: Drosophila model systems. Project Summary: Wolbachia are bacteria that live inside cells of their invertebrate hosts. They are generally maternally transmitted and often spread through populations by manipulating host reproduction. Their most commonly documented reproductive manipulation is "cytoplasmic incompatibility" (CI), increased embryo mortality when infected males mate with uninfected females. CI drives Wolbachia into populations and is being used to introduce into natural mosquito populations Wolbachia strains that suppress disease-causing viruses (particularly dengue fever). With their ability to block pathogen transmission, Wolbachia hold significant promise for controlling many diseases transmitted between humans by insects, including malaria and West Nile virus. Because Wolbachia are maternally inherited, they evolve to help their hosts survive and reproduce, for instance, by suppressing pathogens and increasing host fecundity. Conversely, because Wolbachia reproductive manipulations kill embryos, hosts may evolve to suppress these deleterious effects (without compromising beneficial effects). Health applications of Wolbachia depend on understanding their spread in nature and the potential for rapid Wolbachia-host coevolution. Knowledge of Wolbachia-host interactions in nature is limited to a handful of model systems. Wolbachia infections of Drosophila provide paradigms for understanding rapid spatial spread of Wolbachia, coevolutionary change, and the molecular mechanisms underlying these phenomena. Two of the best understood Wolbachia infections are those in D. simulans (especially wRi) and D. melanogaster (wMel). These infections persist in nature by fundamentally different mechanisms, with only wRi-simulans fully explained. Yet, the wMel-melanogaster association is apparently much older. This project aims to develop a deep understanding of Wolbachia population dynamics and evolution by: (1) expanding field and laboratory analyses of wRi-simulans and wMel-melanogaster, and (2) describing Wolbachia-host interactions and coevolution using at least 30 additional Drosophila species with Wolbachia infections. Tools from genomics, cell biology and evolutionary genetics, already optimized for Drosophila, will be used to study population and evolutionary dynamics in nature. For instance, microinjection techniques will move Wolbachia between Drosophila species and disentangle Wolbachia from host effects. Over the past 20 years, wRi and wMel have spread in Australia, and wRi has evolved in California. These current events provide a unique opportunity to follow population and evolutionary dynamics in action. Over 30 additional Drosophila species, known to carry Wolbachia, will be studied in detail to understand more generally the trajectory, time-scale and mechanisms of coevolution between Wolbachia and their hosts. The proposed research, based on a combination of field surveys, field and laboratory experiments, comparative genomics and lab assays of phenotypic effects, will provide the foundation for understanding likely Wolbachia trajectories in other systems, including applications to mosquito vectors of disease.