Document text
Principal Investigator: Zhijian Jake Tu
Organization: VIRGINIA POLYTECHNIC INST AND ST UNIV
Fiscal Year: 2023
Award: $774,520
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <Aedes><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Assay><Basal Transcription Factor><Basal transcription factor genes><Binding><Bioassay><Biologic Assays><Biological><Biological Assay><Biology><Blood><Blood Reticuloendothelial System><Breakbone Fever Virus><CHIKV><Catalytic Core><Catalytic Domain><Catalytic Region><Catalytic Site><Catalytic Subunit><Cell Communication and Signaling><Cell Signaling><Chikungunya virus><Chromosomes><Code><Coding System><Complex><Culicidae><DENV><DENV vaccine><Dengue><Dengue Vaccine><Dengue Virus><Dengue fever virus><Dengue virus vaccine><Development><Distant><Engineering><Evolution><Eye Color><Female><Flying body movement><Foundations><Functional RNA><Future><General Transcription Factor Gene><General Transcription Factors><Genes><Genome><Gonosomes><Haplotypes><High Throughput Assay><Immune Precipitation><Immunoprecipitation><Insecticide Resistance><Intervening Protein Sequence><Intervening Sequences><Intracellular Communication and Signaling><Introns><Knock-out><Knockout><Knowledge><Laboratories><Link><M Locus><Maintenance><Mediating><Methods><Minor Lymphocyte Stimulatory Loci><Miscellaneous Antibiotic><Mls Loci><Modeling><Molecular Interaction><Mosquito Control><Mosquito-borne disease><Mosquito-borne infectious disease><Mosquitoes><Myosin A><Myosin Heavy Chains><Myosin IIA><Non-Coding><Non-Coding RNA><Non-Muscle Myosin Type IIA><Non-Polyadenylated RNA><Non-translated RNA><Noncoding RNA><Nonmuscle Myosin Type IIA><Nontranslated RNA><Organism><Pathway interactions><Population><Pre-mRNA><Prevention><Production><Property><Protein Introns><Proteins><Pyridoxin><Pyridoxol><RNA><RNA Binding><RNA Editing><RNA Gene Products><RNA Seq><RNA Splicing><RNA bound><RNA sequencing><RNA, Messenger, Editing><RNA, Messenger, Precursors><RNA-Binding Proteins><RNAseq><Recommendation><Research><Ribonucleic Acid><Sex Chromosomes><Sex Differentiation><Signal Transduction><Signal Transduction Systems><Signaling><Splicing><Temperature><Testing><Transcription Factor Proto-Oncogene><Transcription factor genes><Transgenes><Translating><Transmission><Untranslated RNA><VIT B6><Vector-borne disease><Vector-borne infectious disease><Vector-transmitted disease><Vector-transmitted infectious disease><Vitamin B 6><Vitamin B6><Work><Yellow Fever><ZIKA><ZIKV><Zika Virus><adenosine deaminase that acts on RNA><autosome><biologic><biological signal transduction><chikungunya><communicable disease transmission><dADAR><developmental><disease control><disease transmission><disorder control><double-stranded RNA-specific adenosine deaminase><dsRNA adenosine deaminase><dsRNA-specific adenosine deaminase><experiment><experimental research><experimental study><experiments><flying><gene locus><genetic approach><genetic locus><genetic resource><genetic strategy><genomic location><genomic locus><high throughput screening><improved><infectious disease transmission><innovate><innovation><innovative><insecticide resistant><insight><intein><interest><living system><mRNA Precursor><male><myosin heavy chain><noncoding><novel><pathogen><pathway><permissiveness><phenotypic biomarker><phenotypic marker><programs><pyridoxine><rational design><scale up><screening><screenings><sex><sex determination><sex-differentiation><sexual differentiation><synthetic DNA><synthetic construct><transcription factor><transcriptome sequencing><transcriptomic sequencing><transgene><transmission process><vector><vector control><vector-borne illness><vectorborne disease><vectorborne illness><vectorborne infectious disease><zikav>