# Sex ratio distortion in Aedes aegypti

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2021 · $686,260

## Abstract

Project Summary
Aedes aegypti is a major vector of dengue, chikungunya, and Zika viruses. The global incidence of
dengue has increased dramatically in recent decades. The first dengue vaccine, Dengvaxia®, is
recommended for a very limited population. Current prevention depends mainly on effective vector control,
which is hindered by increasing insecticide-resistance. Novel genetic strategies for vector control are
actively explored, including both population suppression and population replacement. Recent field
releases of either transgenic and Wolbachia-infected sterile male mosquitoes show promising results for
suppressing Aedes populations in areas of modest size. Given the biological, geographical, economic
and cultural complexity facing global mosquito-borne infectious disease control programs, diverse
measures that can be integrated to address various challenges are urgently needed. Female to male sex
ratio distortion is an attractive concept for developing new control measures, as females are responsible
for disease transmission and population growth. Aedes and Culex mosquitoes contain homomorphic sex-
determining chromosomes and maleness is conferred by a dominant male-determining factor (M factor)
within an M locus that is on one of a pair of chromosome 1. Male-biased sex-ratio distortion occurs in
natural populations in Ae. aegypti, which is associated with m-chromosome breakage during meiosis at
a few sites. The Distorter locus is linked to the M-locus on the M-chromosome, conferring a meiotic drive
as it increases the probability of its own inheritance. We recently discovered the M factor, an RNA-binding
protein named Nix and identified the M and m locus in Ae. aegypti. By analysing male and female Illumina
reads across a few strains, we found a number of m-specific repeats that can be targeted for breakage
by CRISPR/cas9 during male meiosis, potentially leading to a male-biased sex ratio distortion. We will
pursue the following specific aims: 1) Systematically characterize components to develop m-shredders.
Research performed here will also improve our understanding of the male germline and the homomorphic
sex chromosomes and facilitate any future genetic manipulations involving the male germline. 2) Develop
m-shredder lines with various degrees of M-linkage to optimize effective population suppression. 3)
Model various applications of m-shredders in population suppression and transgene recall. In summary,
innovative technologies will be used to gain fundamental insights into male germline expression and the
differentiation of the homomorphic sex chromosomes of Ae. aegypti. m-shredders with various levels of
efficiency and transmissibility will be developed and modelled for population suppression and transgene
recall, expanding the tool box for integrated vector management.
1

## Key facts

- **NIH application ID:** 10264907
- **Project number:** 5R01AI157491-02
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Zhijian Jake Tu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $686,260
- **Award type:** 5
- **Project period:** 2020-09-16 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10264907

## Citation

> US National Institutes of Health, RePORTER application 10264907, Sex ratio distortion in Aedes aegypti (5R01AI157491-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10264907. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*