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A Mosquito Sex-Determining Gene Could Help Fight Dengue Fever, Life Science Researchers Say

Males aren’t relevant — at least when it comes to disease transmission by mosquitoes.

by Virginia Tech
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male-determining genetic switch in mosquitoesLife scientists identified a male-determining genetic switch called Nix in a dangerous type of mosquito. The discovery could help protect human health.Image credit: Alexander WildResearchers with the Fralin Life Science Institute at Virginia Tech have identified a gene responsible for sex determination in mosquitoes that transmit yellow fever, dengue, and chikungunya viruses.

Only female mosquitoes bite because they need blood for developing eggs, and researchers believe that a higher ratio of males could reduce disease transmission.

In a study published Thursday in Science Express, the scientists identify a male-determining genetic switch called Nix in Aedes aegypti mosquitoes that underlies the difference between males and females. These master switches often reside in genomic black holes, which is why none had been found in mosquitoes or other insects before.

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 “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 scientists injected Nix into mosquito embryos and found more than two-thirds of the female mosquitoes developed male genitals and testes. 

When they removed Nix using a genome-editing method known as CRISPR-Cas9, male mosquitoes developed female genitals.

The study provides the foundation for developing mosquito control strategies by converting females into harmless males or selectively eliminating deadly 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 originally from Africa that first began to spread around the world by ship in the 1700s.  This species is a major health problem because it is highly adapted to human environments.  Aedes aegypti is among the small fraction of mosquito species that transmit pathogens to humans.

“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, from Christiansburg, Virginia, a Ph.D. student in Tu’s lab and co-first author on the paper, together with Sanjay Basu, a postdoctoral associate in Adelman’s lab.

"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 research. “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."

Other authors of the study are Xiaofang Jiang, from Blacksburg, Virginia, a Ph.D. student in the genetics, bioinformatics and computational biology program; Yumin Qi, a research scientist; Vladimir A. Timoshevskiy, a postdoctoral associate; James K. Biedler, a research scientist; Maria V. Sharakhova, a research scientist; Rubayet Elahi, from of Blacksburg, Virginia, a Ph.D. student in biochemistry, Michelle A.E. Anderson, a research technician, Xiao-Guang Chen, a professor at Southern Medical University in Guangdong, China, and Igor Sharakhov, an associate professor of entomology in the College of Agriculture and Life Sciences.