The Genetic Basis of Anthropophily in Anopheles gambiae

描述（由申请人提供）：经过一个多世纪的控制努力，疟疾仍然是最具破坏性的传染病之一。最重要的疟疾媒介是冈比亚按蚊，它的不寻常之处在于它几乎只以人类为食。正是这种强烈的人类习性，在很大程度上导致了这种物种作为疟疾媒介的显著效率。实验室研究表明，安。冈比亚对人类的强烈偏好是基于它对人类气味的吸引力。这种疟疾病媒属于一个密切相关的物种复合体，其中还包括疟蚊。四轮虫，一种很少以人类为食的嗜兽物种。我们将在数量性状位点定位实验中对这两个物种进行回交，以确定基因组中负责吸引An的区域。冈比亚人。接下来，我们将在自然群体中检测所鉴定QTL内的嗅觉基因的遗传变异。这将确定在正选择下进化的嗅觉基因。冈比亚，这可能与适应人类宿主有关。最后，我们将鉴定在An中不同水平表达的QTL内的基因。冈比亚vs.安哥拉。四轮虫雌性嗅觉器官。在这些物种的嗅觉器官中具有较高表达水平的嗅觉基因可能与寄主选择差异有关。我们期望我们的调查将确定负责An的基因。冈比亚对人类的吸引力。阐明宿主偏好的遗传基础不仅将大大增加我们对世界上主要病媒的生物学理解，还将有助于开发新的疟疾控制方法。我们期望亲人基因的鉴定将有助于合理设计更有效的驱蚊/引诱剂，用于个人防护或诱蚊器。重要的是，亲人类基因也可能是转基因控制努力的有希望的目标。一种基因修饰，可以显著降低An的吸引力。冈比亚对人类的影响将对疟疾传播产生重大影响，即使这种转基因并不能完全防止人类吸血。该项目将确定导致世界上最重要的疟疾病媒冈比亚按蚊偏爱吸食人类血液的基因。从流行病学角度来看，这是该物种生物学最重要的方面之一，识别相关基因对于设计新的控制策略具有重要意义。例如，可以设计新的驱蚊剂/引诱剂，专门针对这些人类偏好基因，或者可以通过释放转基因蚊子从自然种群中去除这些基因。

DESCRIPTION (provided by applicant): After more than a century of control efforts, malaria remains one of the most devastating infectious diseases. The most important malaria vector is Anopheles gambiae s.s., which is unusual in that it feeds almost exclusively on humans. It is this strong anthropophily that is largely responsible for this species' remarkable efficiency as a malaria vector. Laboratory studies have shown that An. gambiae's strong preference for humans is based on its attraction to human odor. This malaria vector belongs to a complex of closely related species that also includes An. quadriannulatus, a zoophilic species that rarely feeds on humans. We will backcross these two species in a Quantitative Trait Loci mapping experiment to identify regions of the genome that are responsible for the attraction of An. gambiae to humans. Next, we will examine genetic variation of olfaction genes located inside the identified QTL in natural populations. This will identify those olfaction genes that have evolved under positive selection in An. gambiae, and which are likely involved in the adaptation to human hosts. Finally, we will identify genes inside QTL that are expressed at different levels in An. gambiae vs. An. quadriannulatus female olfactory organs. Olfaction genes which have a relatively high level of expression in the olfactory organs of these species are expected to be involved in the host selection difference. We expect that our investigation will identify genes responsible for An. gambiae's attraction to humans. Elucidating the genetic basis of host preference will not only significantly increase our understanding of the biology of the primary disease vector in the world, it will also contribute to the development of novel malaria control methods. We expect that the identification of anthropophily genes will be useful for the rational design of more efficient repellents/attractants for use in personal protection or mosquito traps. Importantly, anthropophily genes might also be promising targets for transgenic control efforts. A genetic modification that significantly reduces the attraction of An. gambiae to humans would have a major impact on malaria transmission, even if the transgene does not fully prevent blood feeding on humans. PUBLIC HEALTH RELEVANCE This project will identify the genes responsible for the preference of the most important malaria vector in the world, Anopheles gambiae, for blood feeding on humans. This is epidemiologically one of the most important aspects of the biology of this species, and identifying the genes involved is of major importance for designing new control strategies. For example, new repellents/attractants could be designed that specifically target these human preference genes, or these genes could be removed from natural populations by releasing a genetically modified mosquito.