Sex ratio distortion in Aedes aegypti

项目摘要 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。全球范围内的发病率 近几十年来，登革热急剧增加。第一种登革热疫苗登革热® 推荐给非常有限的人群。目前的预防主要依靠有效的媒介控制， 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，包括人口压制和人口置换。新近领域 无论是转基因蚊子还是沃尔巴克氏菌感染的不育雄性蚊子的释放都显示出良好的结果 在中等规模的地区抑制伊蚊种群。鉴于生物的、地理的、经济的 全球蚊媒传染病控制计划面临的文化复杂性，多种多样 迫切需要能够综合起来应对各种挑战的措施。女性对男性 比率扭曲是开发新的控制措施的一个有吸引力的概念，因为女性负有责任 用于疾病传播和人口增长。伊蚊和库蚊含有同态的性别- 决定染色体和男性的决定因素是一个主导的男性决定因素(M因素) 在一对1号染色体上的M基因座内。男性偏见的性别比扭曲发生在 Ae.自然种群。埃及伊蚊，与m-染色体在减数分裂过程中的断裂有关 几个网站。Distorter基因座与M染色体上的M基因座连锁，导致减数分裂驱动 因为它增加了自己继承的可能性。我们最近发现了M因子，一种与RNA结合的因子 命名为Nix的蛋白质，并鉴定了Ae.埃及伊蚊。通过分析雄性和雌性Illumina 通过对几个菌株的阅读，我们发现了一些可以被破坏的m-特异性重复序列 在男性减数分裂过程中，CRISPR/Cas9可能会导致性别比扭曲。我们会 追求以下具体目标：1)系统地表征部件，以开发m-碎纸机。 这里进行的研究也将提高我们对男性生殖系和同态的理解。 并为未来涉及雄性生殖系的任何遗传操作提供便利。2)发展 M-粉碎机品系具有不同程度的M-连锁，以优化有效的种群抑制。3) 模拟m-碎纸机在种群抑制和转基因召回中的各种应用。总而言之， 创新技术将被用来获得对男性生殖系表达和 Ae.同态性染色体的分化。埃及伊蚊。M-碎纸机，具有不同级别的 将开发效率和传播性，并为种群抑制和转基因建立模型 回顾一下，扩大了综合病媒管理的工具箱。 1

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