The male-determining locus of Culex quinquefasciatus

致倦库蚊的雄性决定基因座

基本信息

批准号：
10176411
负责人：
Zhijian Jake Tu
金额：
$ 19.53万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10176411
关键词：
Aedes Anopheles gambiae Basic Science Behavior Behavioral Biology Birds Characteristics Chromosome 1 Chromosome Pairing Complex Control Locus Culex (Genus)Culex pipiens Culicidae Data Data Set Development Ectopic Expression Elements Embryonic Development Encephalitis Viruses Evolution Exhibits Filarial Elephantiases Foundations Genes Genetic Genetic Annotation Genetic study Genome Genomics Glean Goals Homologous Gene Human Inherited Investigation Knock-out Link Mammals Messenger RNA Minor Lymphocyte Stimulatory Loci Molecular Molecular Genetics Mosquito Control Mosquito-borne infectious disease Names Pathway interactions Physiological Population Price Proteins RNA Splicing Reporting Research Resources Sex Bias Sex Chromosomes Sex Ratio Sexual Reproduction Taxon Vectorial capacity West Nile virus base climate change disorder control genetic manipulation genomic locus indexing innovation insight interest male member novel novel strategies scaffold sex sex determination transcriptome sequencing transmission process vector

项目摘要

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.

Culex属中的蚊子是脑炎病毒和淋巴丝虫病蠕虫的主要载体。 Culex Pipiens和C. Quinquefasciatus是西尼罗河病毒的主要媒介，这是现在的主要原因美国大陆（https://www.cdc.gov/westnile/index.html）的蚊子传播疾病。有担忧在西尼罗河病例中，这种气候变化可能会导致进一步增加。 C. pipiens物种复合物的成员，其中包括C. quinquefasciatus，C。pipiens，C。molestus和其他一些物种，显示了不同的模式进化差异和表现出与其媒介能力相关的行为和生理差异。因此，C. pipiens建筑群是从生物医学和基础科学的角度研究。我们对破译男性确定基因座的分子机制具有长期的兴趣（M基因座）控制蚊子中男性生物学的性别确定性和其他方面。我们专注于C。 Quinquefasciatus在这项提案中，既是基本和翻译方面的考虑因素。作为男性确定 C. quinquefasciatus中的因子（M因子）与蚊子中的任何已知M因子不同，新见解将是由新型的Quinquefasciatus中的新型主调节剂管理的性别确定性。提议研究还将为研究基础，以研究同构性染色体的演变并提供父母伴有的标记，以促进对C. pipiens的有趣进化动力学的研究复杂的。从应用的角度来看，拟议的研究将使创新的应用能够控制C。 Quinquefasciatus种群通过引入对非咬人男性的性偏见。通过分析各种RNASEQ数据集，然后进行实验验证，我们最近确定了两个 M基因座中的基因，包括我们称为CMF的新型M因子的强大候选者。我们也获得了高质量的雄性C. quinquefasciatus基因组组装组装，分开父亲和母亲长阅读序列和bionano脚手架。我们将追求两个具体目标：1）系统地表征 M和M基因杆菌在C. quinquefasciatus中的遗传含量； 2）研究选定的M基因座基因的功能包括CMF。该探索性R21将对M和M的遗传含量产生系统注释基因座并发现Quinquefasciatus C. c. c. c. c.c。locus基因的功能。它将奠定基础为了将来研究1）新的M因子的作用机理，2）同构性别的演变染色体，3）M基因座的功能元素，以及基于性别比操纵或与M基因座的联系。