GUY1 confers complete female lethality and is a strong candidate for a male-determining factor in Anopheles stephensi

Abstract
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Abstract

Despite their importance in sexual differentiation and reproduction, Y chromosome genes are rarely described because they reside in repeat-rich regions that are difficult to study. Here, we show that Guy1, a unique Y chromosome gene of a major urban malaria mosquito Anopheles stephensi, confers 100% female lethality when placed on the autosomes. We show that the small GUY1 protein (56 amino acids in length) causes female lethality and that males carrying the transgene are reproductively more competitive than their non-transgenic siblings under laboratory conditions. The GUY1 protein is a primary signal from the Y chromosome that affects embryonic development in a sex-specific manner. Our results have demonstrated, for the first time in mosquitoes, the feasibility of stable transgenic manipulation of sex ratios using an endogenous gene from the male-determining chromosome. These results provide insights into the elusive M factor and suggest exciting opportunities to reduce mosquito populations and disease transmission.

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Frank Criscione

Department of Biochemistry, Virginia Tech, Blacksburg, United States

Competing interests
The authors declare that no competing interests exist.
Yumin Qi

Department of Biochemistry, Virginia Tech, Blacksburg, United States

Competing interests
The authors declare that no competing interests exist.
Zhijian Jake Tu

Department of Biochemistry, Virginia Tech, Blacksburg, United States

For correspondence
jaketu@vt.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-4227-3819

Funding

National Institute of Allergy and Infectious Diseases (AI105575, AI77680, and AI121284)

Zhijian Jake Tu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (#16-067) of Virginia Tech.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.