Author ORCiD
Date of Award
2026
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
Thesis Advisor
Leslie B. Vosshall
Keywords
Aedes aegypti, mosquito, sex-specific RNA splicing, protein evolution, insects
Abstract
Female mosquitoes from many species require a blood meal from an animal host as a protein source for egg development and successful reproduction. The majority of mosquito species are generalists in their host preference, feeding on a range of animals including mammals, birds, and amphibians. However, a small fraction of mosquito species have evolved a preference for human hosts. These species are mainly found in the genera Aedes, Culex, and Anopheles, and they have created a global health crisis due to their ability to transmit deadly human pathogens including dengue virus, Zika virus, West Nile Virus, and the Plasmodium malaria parasite. Understanding the mechanisms that generate these important sexually dimorphic behaviors in mosquitoes is a crucial step towards developing strategies to combat vector borne disease spread. In this work, we investigate the molecular mechanisms of sexually dimorphic behaviors in mosquitoes by characterizing a novel sex-specifically spliced gene called AAEL011211, which was first identified in Aedes aegypti brains and is well conserved in the mosquito lineage. Sex-specific splicing of key genes is a conserved hallmark of genetic regulation of sexual dimorphism in insects. We comprehensively characterize the gene locus and the conserved sex-specific splicing of AAEL011211 in representative species from the mosquito lineage. Additionally, we take advantage of available sex-specific bulk RNA sequencing and single nucleus RNA sequencing data across mosquito tissue to characterize the expression pattern of AAEL011211 in Aedes aegypti. We find that it is enriched in the nervous system and is neuron-specific, suggesting that it may contribute to sexually dimorphic behaviors in the mosquito. We examine the predicted AEEL011211 protein and show that the sex-specific splicing leads to a shorter protein in the female and a longer protein in the male. Homology and phylogenetic analyses show that AAEL011211 proteins have close homologs in the mosquito lineage, distant homologs across the insect tree of life, and no evidence of homologs in vertebrate genomes. While the AAEL011211 proteins have no homology to functionally characterized domains, they are predicted to be nuclear proteins both in mosquitoes and in the distant insect homologs. Moreover, we discover a novel ~200 amino acid domain in AAEL011211, with one copy (D1) in the female protein and two copies (D1 and D2) in the male protein following a domain duplication event. While D1 is found in many insect species, D2 is a male-specific duplication unique to the mosquito lineage, revealing a mosquito-specific sexual dimorphism at the protein level for AAEL011211. The function of AAEL011211is unknown, and future work will be needed to study what role it plays in the unique sexually dimorphic behaviors of mosquitoes. Our characterization of AAEL011211 as a novel conserved mosquito sex-specifically spliced gene expands our knowledge of the potential molecular mechanisms that underlie sexual dimorphism in mosquitoes. Until now, fruitless and doublesex were the only described sex-specifically spliced genes, highlighting the rarity and importance of such regulation. In particular, the neuronal specificity and sex-specific protein domain features of AAEL011211 in mosquitoes suggest that it may function in regulating key female-specific behaviors like host seeking and blood feeding that are central to disease transmission. Future work to understand AAEL011211 may inform and expand the options for vector control strategies aimed at disrupting female-specific behaviors that are critical for pathogen spread.
License and Reuse Information
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
Tsitohay, Yael Norohasimbola, "Evolution of a Novel Neuronal Sex-Specifically Spliced Gene in Mosquitoes" (2026). Student Theses and Dissertations. 847.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/847
Comments
A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy