Last Updated: 29/04/2025
Mechanisms of sex determination in Anopheles and their implementation to control mosquito vectors
Objectives
The objectives of this study are:
- To analyze sex-specific gene expression in Anopheles gambiae using existing high-throughput sequencing datasets across multiple developmental stages;
- To identify genes directly or indirectly regulated by Yob through transcriptomic analysis of genetically modified mosquitoes with Yob inactivation or ectopic expression;
- To functionally characterize candidate sex-determination genes using molecular and genetic approaches;
- To identify and experimentally validate cis-regulatory elements that drive gene expression in early A. gambiae embryos; and
- To contribute to the broader understanding of insect sex determination pathways and inform the development of novel mosquito control strategies through genetic manipulation.
The molecular developmental processes that determine gender in animals are remarkably diverse and often rapidly evolving. As a result, knowledge of sex determination pathways in one species may offer little insight into those of distantly related species. In insects, detailed characterization exists primarily for the fruit fly Drosophila melanogaster, while the mechanisms remain largely unexplored in other groups, including mosquitoes. A male-determining gene, Yob, was recently identified on the Y chromosome of the malaria mosquito Anopheles gambiae. This gene is both necessary for male development and lethal to female embryos when ectopically expressed during early development. However, the molecular mechanisms by which Yob regulates male development and induces female lethality remain unknown.
This study proposes to address these gaps by analyzing high-throughput transcriptomic data collected across developmental stages in A. gambiae, segregated by sex. Sex-specific gene expression patterns will be examined to identify candidate genes potentially involved in sex determination. Concurrently, genetically modified mosquito strains with Yob either inactivated in males or ectopically expressed in females will be analyzed to detect transcriptional changes associated with Yob perturbation. The functional roles of identified genes will be tested using a range of experimental approaches. Additionally, regulatory DNA elements driving early embryonic gene expression will be identified and functionally characterized in transgenic lines. These findings are expected to advance understanding of sex determination in mosquitoes and support the development of genetic vector control strategies by enabling selective female elimination or sex conversion in mosquito populations.
Sep 2017 — Sep 2020
$824,693
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