Sex determination and the sex-determining locus in aedine mosquitoes

摘要 性对于包括蚊子在内的有性繁殖生物的生存和进化至关重要。一个 主导的男性决定因素(M因子)是控制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，是在 蚊子。在一个简化的模型中，预测的RNA结合蛋白Nix的表达导致男性- 两个保守的转录因子Doublesex(DsX)和Numerent的前mRNAs的特异性剪接 (FRU)，它编程男性的性别分化。在伊蚊中，M因子位于雄性体内-- 确定其中一个常染色体上的基因座(M基因座)。这对常染色体就是所谓的 同态的性染色体，在细胞学上是无法区分的，除非在 性爱轨迹。Ae.埃及埃及人M基因座是一个~1.3 Mbp的富含重复序列的区域，它包含Nix和其他四个 蛋白质编码基因和25个长的非编码RNA基因。只有NIX转基因，在没有M的情况下 轨迹，足以将雌性转化为可生育但不会飞的雄性，以及肌性，一种肌球蛋白 链基因也在M基因座上，是男性飞行所必需的。伊蚊的M染色体和M染色体 蚊子提供了一个洞察同型性染色体进化的机会。 除了其基本的生物学意义外，Ae.埃及伊蚊是登革热基孔肯雅热的主要传播媒介， 和寨卡病毒。目前还没有针对登革热的特效治疗方法，建议接种第一种登革热疫苗。 只适用于有限的人口。预防这些媒介传播的传染病在很大程度上依赖于 有效的病媒控制。然而，杀虫剂抗药性的增加构成了一个重大威胁。因此， 迫切需要新的控制策略。只有雌性蚊子以血液为食并传播 病原体和大多数女性决定蚊子种群的大小和分布。 我们感兴趣的是破译性别决定的机制，研究性染色体 进化，并将这些基本知识转化为安全、高效和多样化的控制方法 由Ae传播的疾病。埃及伊蚊。在近期进展的基础上，我们将开展以下工作 具体目标：1)破译《爱》中的性基因。埃及，2)识别和表征NIX的目标(S)， 3)通过NIX媒介的创新，开发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.