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

描述（由申请人提供）：按蚊是疟疾的主要传播媒介，疟疾是人类历史上最致命和最昂贵的疾病之一。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虫叮咬。随着杀虫剂和药物耐药性的增加，这些措施的效果越来越差。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为我们提供了令人兴奋的机会，以前所未有的方式增强了我们对蚊子遗传学、生理学和行为的理解。这一信息将有助于制定防治疟疾和其他蚊媒疾病的新战略。只有雌蚊以血液为食并传播疾病病原体。按蚊使用XX/XY性别测定系统。有证据表明，Y染色体上的显性雄性决定因子启动了按蚊物种的性别分化。遗传学研究表明，昆虫Y染色体参与雄性生殖能力、交配行为和全局基因表达的调控。然而，除了少数模式物种外，Y基因的分子特征是罕见的，这主要是由于Y染色体的重复性质和克隆重复丰富的异色序列的困难。我们最近发现了一些Y基因，包括一个我们称之为Guy1 （Y独有基因）的新基因。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转录，它是一个单拷贝基因，没有常染色体或X平行染色体。我们将验证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敲低（Aim 2）对性别相关表型以及发育和胚胎基因表达的一般变化的影响。这项研究将有助于我们的长期目标，即阐明按蚊性别二型性的遗传基础，并制定相关的和新的控制策略。在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信息。我们期望在R21之外进一步研究Y基因的功能机制，通过Y基因的操作开发蚊虫控制应用，并将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.