If the battle of the sexes was fought by mosquitoes, it would already be over. Researchers from Virginia Tech's Fralin Life Science Institute has discovered that male mosquitoes aren't relevant at all, at least in the realm of transmissible diseases.

The team has identified a gene that determines sex in Aedes aegypti mosquitoes. This variety can be deadly, as it transmits the chikungunya, dengue, and yellow fever viruses. The sex determination gene, called Nix, is significant because only female mosquitoes, who need blood for developing eggs, bite. Researchers think that disease transmission may be reduced if a higher ratio of males can be achieved.

Nix is what is called a master control gene or master switch. These are single genes which must be expressed in order to trigger the activation of some other group of genes in a coordinated way. These master switches are hard to find, because they are often located in the dense centromeres, the so-called genomic black holes. No master switches had been found in insects before Nix, the single gene must be expressed for the mosquito to become male.

"Nix provides us with exciting opportunities to harness mosquito sex in the fight against infectious diseases because maleness is the ultimate disease-refractory trait," said Zhijian Jake Tu, a professor of biochemistry in the College of Agriculture and Life Sciences and a Fralin Life Science Institute affiliate.

The team discovered that more than two-thirds of female mosquitoes developed male testes and genitals when Nix was injected into mosquito embryos. When they used CRISPR-Cas9, a technique for editing genomes, to remove Nix, male mosquitoes developed female genitals. The research sets the stage for mosquito control methods based on sex changes; strategies could either convert females into males, rendering them harmless, or otherwise selectively target females.

"We're not there yet, but the ultimate goal is to be able to establish transgenic lines that express Nix in genetic females to convert them to harmless males," said Zach Adelman, an associate professor of entomology in the College of Agriculture and Life Sciences and a Fralin Life Science affiliate.

Aedes aegypti is an invasive species. It originated in Africa and spread via ship to most of the rest of the world in the 1700s. This adaptive success hints at why this species is so dangerous to humans; it does well in a variety of human environments. Aedes aegypti is one of the few species of mosquitoes that transmit pathogens to human hosts.

"Targeted reduction of Aedes aegypti populations in areas where they are non-native could have little environmental impact, and drastically improve human health," said Brantley Hall, a Ph.D. student in Tu's lab and first author on the paper.

"This work represents a major scientific discovery with considerable implications for applied efforts to control mosquito-borne diseases, including dengue and chikungunya fevers," said Anthony James, a university distinguished professor at the University of California Irvine, who was not involved in the study. "Novel mosquito control efforts based on this gene could push back a number of invasive species that threaten the health and well-being of people in the United States and other areas at risk."

The results were published Thursday in the journal Science Express.