The male-determining locus of Culex quinquefasciatus

库蚊属蚊子是脑炎病毒和淋巴丝虫病蠕虫的主要媒介。库雷克斯 蚊虫和致倦库蚊是西尼罗河病毒的主要媒介，目前西尼罗河病毒是导致人类死亡的主要原因。 美国大陆的蚊媒疾病(https://www.cdc.gov/westnile/index.html).有些人担心 气候变化可能会导致西尼罗河病例进一步增加。淡色库蚊物种复合体的成员， 包括致倦库蚊、淡色库蚊、松材线虫等几种，表现出不同的致病模式。 进化分化，并表现出与它们的媒介能力有关的行为和生理差异。 因此，从生物医学和基础科学的角度对淡色隐翅虫复合体进行研究是很有必要的。 长期以来，我们一直有兴趣破译男性决定基因座的分子机制 (M基因座)控制蚊子的性别决定和雄性生物学的其他方面。我们将重点放在C. 出于基本和翻译两方面的考虑，本提案中的Ququiefasciatus。作为男性决定者 致倦库蚊中的M因子不同于任何已知的蚊子中的M因子，新的见解将是 收集到了由一种新的西洋参主调控器管理的性别决定。建议数 研究还将为研究同态性染色体的进化奠定基础，并提供 父系遗传标记有助于研究令人感兴趣的淡色库蚊的进化动态 很复杂。从应用的角度来看，拟议的研究将使创新的应用程序能够控制C. 通过引入对不咬人雄性的性别偏见，使Ququiefasciatus种群数量增加。 通过分析各种RNAseq数据集并进行实验验证，我们最近确定了两个 M基因座上的基因包括一种新的M因子的有力候选者，我们称之为CMF。我们还获得了一个 分离父本和母本的高质量雄性致倦库蚊基因组组装 序列和Bionano脚手架。我们将追求两个具体目标：1)系统地描述 致倦库蚊M、m基因座的遗传含量；2)研究所选M基因座基因的功能 包括CMF。这一探索性的R21将对M和M的遗传内容产生系统的注释 并发现了最重要的M基因座基因的功能。它将奠定基础 对于1)一种新的M因子的作用机制，2)同态性的进化的进一步研究 染色体，3)m基因座的功能元件，以及4)基于性别比操纵或 与M基因连锁。

Mosquitoes in the Culex genus are principal vectors of encephalitis viruses and lymphatic filariasis worms. Culex pipiens and C. quinquefasciatus are major vectors of West Nile virus, which is now the leading cause of mosquito-borne disease in the continental US (https://www.cdc.gov/westnile/index.html). There are concerns that climate change may cause further increases in West Nile cases. Members of the C. pipiens species complex, which includes C. quinquefasciatus, C. pipiens, C. molestus and a few other species, show different modes of evolutionary divergence and exhibit behavioral and physiological differences relevant to their vectorial capacity. Therefore, the C. pipiens complex are compelling to study from both biomedical and basic science perspectives. We have a long-standing interest in deciphering the molecular mechanisms by which the male-determining locus (M locus) controls sex-determination and other aspects of male biology in mosquitoes. We focus on C. quinquefasciatus in this proposal for both fundamental and translational considerations. As the male-determining factor (M factor) in C. quinquefasciatus is different from any known M factors in mosquitoes, new insights will be gleaned into sex-determination governed by a novel master regulator in C. quinquefasciatus. The proposed research will also lay the foundation for studies into the evolution of homomorphic sex chromosomes and provide paternally-inherited markers to facilitate investigations into the intriguing evolutionary dynamics of the C. pipiens complex. From an applied perspective, the proposed research will enable innovative applications to control C. quinquefasciatus populations through the introduction of a sex bias towards the non-biting males. By analyzing various RNAseq datasets followed by experimental verifications, we have recently identified two genes in the M locus including a strong candidate for a novel M factor we named cMf. We have also obtained a high quality male C. quinquefasciatus genome assembly by separating paternal and maternal long-read sequences and by Bionano scaffolding. We will pursue two specific aims: 1) systematically characterize the genetic contents of the M and m loci in C. quinquefasciatus; 2) investigate the function of selected M locus genes including cMf. This exploratory R21 will produce a systematic annotation of the genetic contents of the M and m loci and discover the function of the most important M locus genes in C. quinquefasciatus. It will lay the foundation for future research into 1) the mechanism of action of a novel M factor, 2) the evolution of the homomorphic sex chromosomes, 3) the functional elements of the m locus, and 4) applications based on sex ratio manipulation or linkage to the M locus.