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Nat Commun. 2014 Jun 10;5:3977. doi: 10.1038/ncomms4977.

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

Author information

1
1] Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK [2] Centro di Genomica Funzionale, University of Perugia, Dipartimento di Medicina Sperimentale Via Gambuli, Edificio D, 3° Piano, 06132 Perugia, Italy.
2
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
3
Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
4
1] Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK [2].
5
1] Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK [2] Centro di Genomica Funzionale, University of Perugia, Dipartimento di Medicina Sperimentale Via Gambuli, Edificio D, 3° Piano, 06132 Perugia, Italy [3].

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.

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PMID:
24915045
PMCID:
PMC4057611
DOI:
10.1038/ncomms4977
[Indexed for MEDLINE]
Free PMC Article

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