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.
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DOI:
10.1038/ncomms4977
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发表时间:
2014-06-10
影响因子:
16.6
通讯作者:
Crisanti A
Crisanti A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Galizi R;Doyle LA;Menichelli M;Bernardini F;Deredec A;Burt A;Stoddard BL;Windbichler N;Crisanti A

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理论上,诱导极端的生殖性别比可能是抑制或消除害虫种群的一种方法。对自然发生的性扭曲因子的遗传组成和作用模式以及共同进化抑制因子的普遍存在的有限知识阻碍了它们用于控制。在这里,我们通过利用归巢内切酶I-PpoI的特异性来产生一个合成性扭曲系统,它能够选择性地切割疟疾媒介冈比亚按蚊的核糖体基因序列,这些基因序列只位于蚊子的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来限制潜在毒性的核酸内切酶对精子发生的活性。父系X染色体的粉碎阻止了它传递给下一代,导致了完全可以生育的蚊子品系,产生了95%的雄性后代。我们证明了扭曲雄性蚊子可以有效地抑制笼子里的野生型蚊子种群,为一类新的遗传媒介控制策略提供了基础。极端的生殖性别比可能导致害虫种群的抑制或消灭。在这里,作者设计了一种在冈比亚按蚊中合成的性别扭曲系统,它可以产生可生育的蚊子品系,产生超过95%的雄性后代,因此可以用来抑制蚊子数量。
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. Extreme reproductive sex ratios could result in the suppression or elimination of pest populations. Here, the authors design a synthetic sex distortion system in Anopheles gambiae that gives rise to fertile mosquito strains that produce over 95% male offsprings and could therefore be used to suppress mosquito populations.
DOI: 10.1038/nmeth.2649
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