Galizi Roberto, Doyle Lindsey A, Menichelli Miriam, Bernardini Federica, Deredec Anne, Burt Austin, Stoddard Barry L, Windbichler Nikolai, Crisanti Andrea
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.
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Nat Commun. 2014 Jun 10;5:3977. doi: 10.1038/ncomms4977.
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.
从理论上来说，诱导产生极端的生殖性别比例可能是一种抑制或消灭害虫种群的方法。对于自然发生的性别扭曲因子的基因组成和作用方式以及共同进化的抑制因子的流行情况了解有限，这阻碍了它们在害虫控制中的应用。在此，我们利用归巢内切酶I-PpoI的特异性构建了一个合成性别扭曲系统，该酶能够选择性地切割疟蚊冈比亚按蚊的核糖体基因序列，这些序列仅位于蚊子的X染色体上。我们结合基于结构的蛋白质工程和分子遗传学，将潜在有毒的内切酶的活性限制在精子发生过程中。父本X染色体的断裂阻止了它传递给下一代，从而产生了完全可育的蚊子品系，其产生的雄性后代超过95%。我们证明，携带性别扭曲因子的雄蚊能够有效地抑制封闭环境中的野生型蚊子种群，为一类新的遗传媒介控制策略奠定了基础。
