A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae

A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae
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DOI:
10.1038/s41587-020-0508-1
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发表时间:
2020-05-11
影响因子:
46.9
通讯作者:
Crisanti, Andrea
Crisanti, Andrea
中科院分区:
工程技术1区
文献类型:
--
作者:
Simoni, Alekos;Hammond, Andrew M.;Crisanti, Andrea

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一种性别扭曲基因驱动导致了疟疾蚊子的种群崩溃。只有雌性昆虫才能传播疟疾、登革热和寨卡等疾病;因此,长期以来一直在寻找使昆虫后代性别比例发生偏差的控制方法。性染色体驱动等遗传因素可以扭曲性别比例,产生最终崩溃的中性种群,但潜在的分子机制尚不清楚。我们报告了一个男性偏见的性别扭曲基因驱动(SDGD)在人类疟疾载体冈比亚按蚊。我们通过将其与插入doublemex(dsx)基因保守序列中的基于CRISPR的基因驱动器偶联,诱导了X染色体切割I-PpoI核酸酶的超孟德尔遗传。在入侵动力学建模中,SDGD被预测对雌性蚊子种群的影响比以前开发的针对雌性生育力的基因驱动更快。dsx基因座的SDGD导致在10-14代中从2.5%的起始等位基因频率产生仅雄性群体,群体崩溃并且没有抗性选择。我们的研究结果支持使用SDGD疟疾病媒控制。
A sex-distorter gene drive causes population collapse in the malaria mosquito.Only female insects transmit diseases such as malaria, dengue and Zika; therefore, control methods that bias the sex ratio of insect offspring have long been sought. Genetic elements such as sex-chromosome drives can distort sex ratios to produce unisex populations that eventually collapse, but the underlying molecular mechanisms are unknown. We report a male-biased sex-distorter gene drive (SDGD) in the human malaria vector Anopheles gambiae. We induced super-Mendelian inheritance of the X-chromosome-shredding I-PpoI nuclease by coupling this to a CRISPR-based gene drive inserted into a conserved sequence of the doublesex (dsx) gene. In modeling of invasion dynamics, SDGD was predicted to have a quicker impact on female mosquito populations than previously developed gene drives targeting female fertility. The SDGD at the dsx locus led to a male-only population from a 2.5% starting allelic frequency in 10-14 generations, with population collapse and no selection for resistance. Our results support the use of SDGD for malaria vector control.