The Genetic Basis of Anthropophily in Anopheles gambiae

描述(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，它的不同寻常之处在于它几乎完全以人类为食。正是这种强大的人类性在很大程度上造就了该物种作为疟疾媒介的非凡效率。实验室研究表明，An.冈比亚对人类的强烈偏好是基于它对人类气味的吸引力。这种疟疾媒介属于一个密切相关物种的复合体，其中也包括一种。四环鱼，一种嗜食动物的物种，很少以人类为食。我们将在数量性状基因座定位实验中回交这两个物种，以确定基因组中负责吸引An的区域。冈比亚对人类的影响。接下来，我们将检查位于已识别的QTL内的自然群体中嗅觉基因的遗传变异。这将识别那些在正选择下进化的嗅觉基因。冈比亚，它们可能参与了对人类宿主的适应。最后，我们将确定QTL中在不同水平上表达的基因。冈比亚亚纲VS An.四环龙雌性嗅觉器官。在这些物种的嗅觉器官中表达水平相对较高的嗅觉基因可能参与了寄主选择的差异。我们预计，我们的调查将确定导致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显著增加我们对世界上主要疾病媒介生物学的了解，还将有助于开发新的疟疾控制方法。我们期望人类基因的鉴定将有助于合理设计更有效的驱蚊剂/引诱剂，用于个人防护或蚊子诱捕器。重要的是，人类基因也可能成为转基因控制努力的目标。一种基因修饰，它显著降低了一只蚂蚁的吸引力。冈比亚对人类的传播将对疟疾传播产生重大影响，即使转基因不能完全阻止血液喂养人类。公共卫生意义该项目将确定导致世界上最重要的疟疾媒介冈比亚按蚊偏爱以人类为食的基因。从流行病学上讲，这是该物种生物学中最重要的方面之一，识别相关基因对于设计新的控制策略具有重要意义。例如，可以专门针对这些人类偏好基因设计新的驱避剂/引诱剂，或者通过释放转基因蚊子将这些基因从自然种群中移除。

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.