Department of Life Sciences, Imperial College London, London, UK.
Polo d'Innovazione Genomica, Genetica e Biologia, Terni, Italy.
Nat Biotechnol. 2020 Sep;38(9):1054-1060. doi: 10.1038/s41587-020-0508-1. Epub 2020 May 11.
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.
只有雌性昆虫传播疟疾、登革热和寨卡等疾病;因此,长期以来一直寻求偏向昆虫后代性别比例的控制方法。性染色体驱动等遗传元件可以扭曲性别比例,产生最终会崩溃的雌雄同体种群,但潜在的分子机制尚不清楚。我们在人类疟疾传播媒介冈比亚按蚊中报告了一种偏雄性的性分配器基因驱动(SDGD)。我们通过将这种基因驱动与插入到 doublesex(dsx)基因保守序列中的基于 CRISPR 的基因驱动结合起来,诱导 X 染色体碎裂的 I-PpoI 核酸内切酶的超 Mendelian 遗传。在入侵动力学建模中,SDGD 预计比以前针对雌性生育力的基因驱动对雌性蚊子种群产生更快的影响。dsx 基因座上的 SDGD 在 10-14 代内从 2.5%的起始等位基因频率导致仅雄性种群,种群崩溃且没有选择抗性。我们的结果支持将 SDGD 用于疟疾媒介控制。