A synthetic sex ratio distortion system for the control of the human malaria mosquito

Roberto Galizi, Lindsey A. Doyle, Miriam Menichelli, Federica Bernardini, Anne Deredec, Austin Burt, Barry L. Stoddard, Nikolai Windbichler () and Andrea Crisanti ()
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Roberto Galizi: Imperial College London, South Kensington Campus
Lindsey A. Doyle: Fred Hutchinson Cancer Research Center
Miriam Menichelli: Imperial College London, South Kensington Campus
Federica Bernardini: Imperial College London, South Kensington Campus
Anne Deredec: Imperial College London, South Kensington Campus
Austin Burt: Imperial College London, South Kensington Campus
Barry L. Stoddard: Fred Hutchinson Cancer Research Center
Nikolai Windbichler: Imperial College London, South Kensington Campus
Andrea Crisanti: Imperial College London, South Kensington Campus

Nature Communications, 2014, vol. 5, issue 1, 1-8

Abstract: Abstract It has been theorized that inducing extreme reproductive sex ratios could be a method to suppress or eliminate pest populations. Limited knowledge about the genetic makeup and mode of action of naturally occurring sex distorters and the prevalence of co-evolving suppressors has hampered their use for control. Here we generate a synthetic sex distortion system by exploiting the specificity of the homing endonuclease I-PpoI, which is able to selectively cleave ribosomal gene sequences of the malaria vector Anopheles gambiae that are located exclusively on the mosquito’s X chromosome. We combine structure-based protein engineering and molecular genetics to restrict the activity of the potentially toxic endonuclease to spermatogenesis. Shredding of the paternal X chromosome prevents it from being transmitted to the next generation, resulting in fully fertile mosquito strains that produce >95% male offspring. We demonstrate that distorter male mosquitoes can efficiently suppress caged wild-type mosquito populations, providing the foundation for a new class of genetic vector control strategies.

Date: 2014
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DOI: 10.1038/ncomms4977

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