title: A synthetic sex ratio distortion system for the control of the human malaria mosquito.
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.
authors.affiliation: 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.
authors.forename: Roberto
authors.initials: R
authors.lastname: Galizi
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Doyle
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Miriam
authors.initials: M
authors.lastname: Menichelli
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Federica
authors.initials: F
authors.lastname: Bernardini
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Deredec
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Austin
authors.initials: A
authors.lastname: Burt
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Barry L
authors.initials: BL
authors.lastname: Stoddard
authors.affiliation: 1] Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK [2].
authors.forename: Nikolai
authors.initials: N
authors.lastname: Windbichler
authors.affiliation: 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].
authors.forename: Andrea
authors.initials: A
authors.lastname: Crisanti
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000852:Anopheles / Q000235:genetics / Q000469:parasitology*; D005260:Female; D007303:Insect Vectors; D008288:Malaria / Q000635:transmission*; D008297:Male; D009032:Mosquito Control; D012744:Sex Ratio; D014960:X Chromosome