The Genetic Basis of Anthropophily in Anopheles gambiae

描述（由申请人提供）：经过世纪的控制努力，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，这很不寻常因为它几乎只以人类为食正是这种强烈的寄生性，在很大程度上是该物种作为疟疾媒介的显著效率的原因。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的复合体，其中也包括An。quadriannulatus，一种很少以人类为食的动物物种。我们将在数量性状基因定位实验中回交这两个物种，以确定负责吸引An的基因组区域。冈比亚人。接下来，我们将研究自然群体中位于所确定的QTL内的嗅觉基因的遗传变异。这将确定那些嗅觉基因，在积极的选择下进化的An。冈比亚，并可能参与适应人类宿主。最后，我们将确定QTL内的基因，在不同的水平上表达的一个。冈比亚与安quadriannulatus雌性嗅觉器官。嗅觉基因在这些物种的嗅觉器官中有相对高水平的表达，预计参与寄主选择差异。我们希望我们的研究将确定基因负责安。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疾病媒介生物学的理解，还将有助于开发新的疟疾控制方法。我们希望，识别的arphilily基因将是有用的，更有效的驱避剂/引诱剂的合理设计，用于个人保护或蚊子陷阱。重要的是，亲脂基因也可能是转基因控制工作的有希望的目标。一种基因改造，大大降低了安的吸引力。即使转基因不能完全防止人类吸血，冈比亚的转基因对人类的疟疾传播也会产生重大影响。

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.