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

史氏按蚊 Y 特异性基因 Guy1 的功能

• 批准号: 8492308
• 负责人: Zhijian Jake Tu
• 金额: $ 23.45万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-15 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8492308
• 关键词: Anopheles Genus; Attention; Behavior; Bite; Blood; Chromosomes; Cloning; Communicable Diseases; Complement; Complementary DNA; Coupling; Culicidae; DNA; Data; Deposition; Development; Diagnosis; Disease; Drosophila melanogaster; Drug resistance; Embryo; Embryonic Development; Ensure; Evolution; Exposure to; Female; Fertility; Future; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Genomics; Human; Injection of therapeutic agent; Insecta; Insecticide Resistance; Insecticides; Investigation; Laboratories; Length; Malaria; Measures; Messenger RNA; Methods; Middle East; Modeling; Molecular; Monitor; Mosquito Control; Mosquito-borne infectious disease; Nature; Outcome; Parasites; Partner in relationship; Pharmaceutical Preparations; Phenotype; Phylogenetic Analysis; Physiology; Population; Recording of previous events; Regulation; Research; Reverse Transcriptase Polymerase Chain Reaction; Sex Behavior; Signal Transduction; Site; Spermatogenesis; System; Technology; Testing; Time; Transgenes; Transgenic Organisms; Vaccines; Work; Y Chromosome; base; combat; egg; experience; exposed human population; feeding; fly; gene function; genetic manipulation; improved; knock-down; male; next generation sequencing; novel; novel marker; novel strategies; paralogous gene; pathogen; promoter; public health relevance; research study; sex; sex determination; sexual dimorphism; transcriptome sequencing; vector

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.

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代价最高的疾病之一。尽管正在测试有希望的候选疫苗，但目前还没有有效的疟疾疫苗。目前的控制策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的机会。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。迫切需要控制疟疾的新方法。最近新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，以以前难以想象的方式增强我们对蚊子遗传学、生理学和行为的理解。这些信息将有助于制定抗击疟疾和其他蚊媒疾病的新战略。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 染色体上的显性雄性决定因子启动按蚊物种的性别分化。遗传学研究表明，昆虫 Y 染色体参与雄性生育力、交配行为和整体基因表达的调节。然而，除了少数模型物种之外，Y 基因的分子特征很少见，这主要是由于 Y 染色体的重复性质以及克隆富含重复的异染色质序列的困难。我们最近发现了一些 Y 基因，其中包括一个我们称为 Guy1（Y 独有的基因）的新基因。我们选择在这个 R21 项目中研究 Guy1 的功能，因为 Guy1 在早期胚胎中合子转录一开始就被转录，并且它是一个单拷贝基因，没有常染色体或 X 旁系同源物。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（目标 1）和 Guy1 敲低（目标 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，即阐明按蚊性别二态性的遗传基础，并制定相关的新控制策略。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。我们期望超越 R21 来研究 Y 基因功能的机制，通过操纵 Y 基因开发蚊子控制应用，并将 Y 基因建立为系统发育、种群和交配行为研究的新标记。