Sex determination and the sex-determining locus in aedine mosquitoes

摘要 性对于包括蚊子在内的有性生殖生物的生存和进化至关重要。一 显性雄性决定因子（M因子）是控制雄性生殖系统性别决定的主要信号。 蚊子Nix是黄热病蚊子埃及伊蚊中的M因子，是第一个发现的M因子。 蚊子在一个简化的模型中，Nix（一种预测的RNA结合蛋白）的表达导致雄性- 特异性剪接两个保守的转录因子，doublyex（dsx）和fruitless (fru)这是一个男性性别分化的程序。在伊蚊中，M因子位于雄性体内- 决定基因座（M基因座）的“常染色体”之一。这对“常染色体”就是所谓的 同型性染色体，细胞学上除了染色体周围的区域外无法区分。 性位点的Ae。埃及伊蚊M基因座是一个约1.3Mbp的重复序列富集区，包含Nix和其他四个基因， 蛋白质编码和25个长的非编码RNA基因。单独的Nix转基因，在M 基因座，足以将女性转化为肥沃的，虽然不会飞的男性，和myo-sex，一个肌球蛋白重 链基因也在M位点，是雄性飞行所必需的。伊蚊的带M染色体和带M染色体 蚊子提供了一个深入了解同形性染色体进化的机会。 除了其基本的生物学重要性，Ae。埃及伊蚊是登革热，基孔肯雅热， 寨卡病毒目前还没有针对登革热的特异性治疗方法，建议接种第一种登革热疫苗 只针对有限的人群。预防这些病媒传播的传染病主要依靠 有效的病媒控制。然而，不断增加的耐药性构成了重大威胁。因此，我们认为， 迫切需要新的控制策略。只有雌性蚊子以血为食并传播 病原体，而且在大多数情况下，雌性蚊子决定了蚊子种群的大小和分布。 我们对性别决定机制的破译、性染色体的研究都很感兴趣 进化，并将这些基本知识转化为安全，有效和多样化的方法来控制 由Ae传播的疾病。埃及人。在最近取得的进展的基础上，我们将继续开展以下工作 具体目标：1）破译Ae.埃及，2）识别和表征尼克斯的目标， （3）通过Nix介导的创新发展有效的性别分离方法。

Abstract Sex is critical to the survival and evolution of sexually reproducing organisms including mosquitoes. A dominant male-determining factor (M factor) is the primary signal that controls sex-determination in mosquitoes. Nix, the M factor in the yellow fever mosquito Aedes aegypti, is the first M factor found in mosquitoes. In a simplified model, the expression of Nix, a predicted RNA-binding protein, leads to male- specific splicing of the pre-mRNAs of two conserved transcription factors, doublesex (dsx) and fruitless (fru), which program male sexual differentiation. In Aedes the M factor is located within the male- determining locus (M locus) on one of the “autosomes”. This pair of “autosomes” are so-called homomorphic sex chromosomes that are cytologically indistinguishable except in the region around the sex locus. The Ae. aegypti M locus is a ~1.3 Mbp repeat-rich region that contains Nix and four other protein-coding and 25 long non-coding RNA genes. The Nix transgene alone, in the absence of the M locus, is sufficient to convert females into fertile albeit flightless males, and myo-sex, a myosin heavy chain gene also in the M-locus, is required for male flight. The M- and m-bearing chromosomes in Aedes mosquitoes provide an opportunity to gain insights into the evolution of homomorphic sex chromosomes. In addition to its basic biological importance, Ae. aegypti is a major vector for the dengue, chikungunya, and Zika viruses. No specific treatment for dengue exists and the first dengue vaccine is recommended only for a limited population. Prevention of these vector-borne infectious diseases relies heavily on effective vector control. However, increasing insecticide-resistance poses a significant threat. Therefore, novel control strategies are urgently needed. Only female mosquitoes feed on blood and transmit pathogens, and for the most part females determine the size and distribution of the mosquito population. We are interested in deciphering the mechanism of sex-determination, investigating sex chromosome evolution, and translating such fundamental knowledge into safe, efficient, and diverse methods to control diseases that are transmitted by Ae. aegypti. Building on recent progress, we will pursue the following specific aims: 1) Decipher the sex locus in Ae. aegypti, 2) Identify and characterize the target(s) of Nix, and 3) Develop efficient sex-separation methods through Nix-mediated innovations.