A synthetic sex ratio distortion system for the control of the human malaria mosquito
A synthetic sex ratio distortion system for the control of the human malaria mosquito
Tags: Gene drive mechanisms, Gene drive synthetic, Other arthropods, Replicator/site directed nuclease, Y-chromosomeGalizi, RD, L. A.; Menichelli, M.; Bernardini, F.; Deredec, A.; Burt, A.; Stoddard, B. L.; Windbichler, N.; Crisanti, A., Nature Communications, 5:3977. 2014.
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.