Function of Guy1, a Y-specific gene of Anopheles stephensi

描述(申请人提供)：按蚊是疟疾的主要媒介，疟疾是人类历史上最致命和代价最高的疾病之一。目前还没有有效的疟疾疫苗，尽管有希望的候选疫苗正在进行测试。目前的控制战略依赖于及时诊断和药物治疗，以及减少人类接触传染性蚊子叮咬的机会。随着杀虫剂和抗药性的增加，这些措施正在变得不那么有效。迫切需要新的疟疾控制方法。最近下一代测序技术在蚊子基因组学中的应用提供了令人兴奋的机会，以以前无法想象的方式加强我们对蚊子遗传学、生理学和行为的了解。这些信息将使制定防治疟疾和其他蚊媒疾病的新战略成为可能。只有雌性蚊子以血液为食并传播疾病病原体。按蚊使用XX/XY性别决定系统。有证据表明，Y染色体上的一个显性男性决定因子(S)启动了按蚊物种的性别分化。遗传学研究表明，昆虫Y染色体参与了雄性生育、交配行为和全球基因表达的调节。然而，除了少数模式物种外，Y基因的分子特征很少见，主要是由于Y染色体的重复性质和克隆富含重复序列的异染色质序列的困难。我们最近发现了一些Y基因，包括一种新的基因，我们称之为Guy1(Y独有的基因)。我们选择在这个R21项目中研究Guy1的功能，因为Guy1在早期胚胎的合子转录开始时就被转录，并且它是一个单拷贝基因，没有常染色体或X平行序列。我们将检验Guy1参与早期胚胎性别分化的假设。我们将研究异位Guy1表达(Aim 1)和Guy1基因敲除(Aim 2)对性别相关表型的影响，以及发育和胚胎基因表达的一般变化。这项研究将有助于我们的长期目标，即阐明按蚊性二型性的遗传基础，并开发相关的新的控制策略。这项研究中开发的方法将为其他按蚊物种的未来工作提供参考。我们期望在R21之外进一步研究Y基因的功能机制，通过操纵Y基因来开发蚊子控制应用，并建立Y基因作为系统发育、种群和交配行为研究的新标记。

DESCRIPTION (provided by applicant): Anopheles mosquitoes are the primary vectors of malaria, one of the most deadly and costly diseases in human history. There is no effective vaccine against malaria, although promising candidates are being tested. Current control strategies rely on prompt diagnosis and drug treatment and the reduction of human exposure to infectious mosquito bites. These measures are becoming less effective as insecticide- and drug-resistance increases. Novel approaches to malaria control are urgently needed. Recent application of next-generation sequencing technologies to mosquito genomics offers exciting opportunities to enhance our understanding of mosquito genetics, physiology, and behavior, in ways that were previously unimaginable. This information will enable the development of new strategies to combat malaria and other mosquito-borne diseases. Only female mosquitoes feed on blood and transmit disease pathogens. Anopheles mosquitoes use the XX/XY sex-determination system. There is evidence that a dominant male-determining factor(s) on the Y chromosome initiates sexual differentiation in an Anopheles species. Genetic studies show that insect Y chromosomes are involved in the regulation of male fertility, mating behavior, and global gene expression. However, molecular characterizations of Y genes are rare outside of a few model species, mostly due to the repetitive nature of the Y chromosome and the difficulty of cloning repeat-rich heterochromatic sequences. We have recently discovered a few Y genes including a novel gene we call Guy1 (Gene Unique to Y). We choose to investigate the function of Guy1 in this R21 project because Guy1 is transcribed at the very onset of zygotic transcription in the early embryo and it is a single copy gene with no autosomal or X paralog. We will test the hypothesis that Guy1 is involved in sexual differentiation in the early embryo. We will investigate the effect of ectopic Guy1 expression (Aim 1) and Guy1 knockdown (Aim 2) on sex-related phenotypes as well as general changes in development and embryonic gene expression. This research will contribute to our long-term objective, which is to illuminate the genetic basis of sexual dimorphism in anopheline mosquitoes and develop relevant and new control strategies. The approach developed in this research will inform future work in other Anopheles species. We anticipate extending beyond this R21 to investigate the mechanism of Y gene function, develop mosquito control applications through the manipulation of Y genes, and establish Y genes as novel markers for phylogenetic, population and mating behavior studies.