Sex ratio distortion in Aedes aegypti

埃及伊蚊性别比例扭曲

• 批准号: 10681401
• 负责人: Zhijian Jake Tu
• 金额: $ 56.66万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-16 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10681401
• 关键词: Address; Aedes; Anopheles gambiae; Area; Biological; CRISPR/Cas technology; Cells; Chikungunya virus; Chromatin; Chromosome 1; Chromosome Breakage; Chromosome Pairing; Chromosomes; Culex (Genus); Culicidae; Dengue; Dengue Vaccine; Dengue Virus; Dengvaxia; Disease Outbreaks; Economics; Equilibrium; Female; Future; Gene Targeting; Genes; Genetic Transcription; Geography; Haplotypes; Incidence; Insecticide Resistance; Laboratories; Link; Male Sterility; Male Sterilizations; Measures; Meiosis; Methods; Minor Lymphocyte Stimulatory Loci; Mitosis; Modeling; Molecular; Mosquito Control; Mosquito-borne infectious disease; Myeloma Proteins; Names; Population; Population Growth; Population Replacements; Prevention; Probability; Property; RNA-Binding Proteins; Recommendation; Research; Resistance; Sex Bias; Sex Chromosomes; Sex Differences; Sex Ratio; Site; Specificity; Split Genes; Surveys; System; Testing; Time; Transgenes; Transgenic Organisms; Wolbachia; Wood material; X Chromosome; Y Chromosome; ZIKA; Zika Virus; active control; autosome; chikungunya; cost; disease transmission; disorder control; fitness; genetic approach; genetic manipulation; improved; innovation; innovative technologies; insight; male; novel; programs; promoter; prototype; sex; sperm cell; tool; transgene expression; transmission process; vector; vector control; vector management strategies

Project Summary Aedes aegypti is a major vector of dengue, chikungunya, and Zika viruses. The global incidence of dengue has increased dramatically in recent decades. The first dengue vaccine, Dengvaxia®, is recommended for a very limited population. Current prevention depends mainly on effective vector control, which is hindered by increasing insecticide-resistance. Novel genetic strategies for vector control are actively explored, including both population suppression and population replacement. Recent field releases of either transgenic and Wolbachia-infected sterile male mosquitoes show promising results for suppressing Aedes populations in areas of modest size. Given the biological, geographical, economic and cultural complexity facing global mosquito-borne infectious disease control programs, diverse measures that can be integrated to address various challenges are urgently needed. Female to male sex ratio distortion is an attractive concept for developing new control measures, as females are responsible for disease transmission and population growth. Aedes and Culex mosquitoes contain homomorphic sex- determining chromosomes and maleness is conferred by a dominant male-determining factor (M factor) within an M locus that is on one of a pair of chromosome 1. Male-biased sex-ratio distortion occurs in natural populations in Ae. aegypti, which is associated with m-chromosome breakage during meiosis at a few sites. The Distorter locus is linked to the M-locus on the M-chromosome, conferring a meiotic drive as it increases the probability of its own inheritance. We recently discovered the M factor, an RNA-binding protein named Nix and identified the M and m locus in Ae. aegypti. By analysing male and female Illumina reads across a few strains, we found a number of m-specific repeats that can be targeted for breakage by CRISPR/cas9 during male meiosis, potentially leading to a male-biased sex ratio distortion. We will pursue the following specific aims: 1) Systematically characterize components to develop m-shredders. Research performed here will also improve our understanding of the male germline and the homomorphic sex chromosomes and facilitate any future genetic manipulations involving the male germline. 2) Develop m-shredder lines with various degrees of M-linkage to optimize effective population suppression. 3) Model various applications of m-shredders in population suppression and transgene recall. In summary, innovative technologies will be used to gain fundamental insights into male germline expression and the differentiation of the homomorphic sex chromosomes of Ae. aegypti. m-shredders with various levels of efficiency and transmissibility will be developed and modelled for population suppression and transgene recall, expanding the tool box for integrated vector management. 1

项目概要 埃及伊蚊是登革热、基孔肯雅热和寨卡病毒的主要传播媒介。全球发病率 近几十年来，登革热急剧增加。第一种登革热疫苗 Dengvaxia® 是 推荐给非常有限的人群。当前的预防主要依靠有效的病媒控制， 这是由于杀虫剂抗药性的增加而受到阻碍。用于病媒控制的新遗传策略是 积极探索，包括人口抑制和人口替代。最近的领域 转基因和感染沃尔巴克氏体的不育雄性蚊子的释放显示出有希望的结果 抑制中等面积地区的伊蚊种群。鉴于生物、地理、经济 全球蚊媒传染病控制计划面临的文化复杂性、多样性 迫切需要采取综合措施来应对各种挑战。女性对男性性别 比例扭曲对于制定新的控制措施来说是一个有吸引力的概念，因为女性负有责任 疾病传播和人口增长。伊蚊和库蚊具有同形性 决定染色体和雄性的因素是由显性的雄性决定因子（M 因子）赋予的 位于一对染色体 1 之一上的 M 基因座内。男性偏向的性别比例扭曲发生在 Ae 的自然种群。埃及伊蚊，与减数分裂期间的 m 染色体断裂有关 一些网站。 Distorter 基因座与 M 染色体上的 M 基因座相连，赋予减数分裂驱动力 因为它增加了自己继承的可能性。我们最近发现了 M 因子，一种 RNA 结合因子 蛋白质命名为 Nix，并鉴定了 Ae 中的 M 和 m 基因座。埃及伊蚊。通过分析男性和女性 Illumina 读取几个菌株后，我们发现了许多 m 特异性重复序列，可以作为断裂的目标 在雄性减数分裂过程中通过 CRISPR/cas9，可能导致偏向雄性的性别比例扭曲。我们将 追求以下具体目标： 1) 系统地表征开发 m-粉碎机的组件。 这里进行的研究还将提高我们对雄性种系和同态性的理解 性染色体并促进未来涉及雄性种系的遗传操作。 2）开发 m-粉碎机系列具有不同程度的 M-联动，可优化有效的群体抑制。 3） 对 m-粉碎机在群体抑制和转基因召回中的各种应用进行建模。总之， 将使用创新技术来获得对雄性种系表达和 Ae同态性染色体的分化。埃及伊蚊。具有不同级别的 m-粉碎机 将开发效率和传播性并为种群抑制和转基因建模 回顾一下，扩展了综合病媒管理的工具箱。 1