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.

中文翻译：

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人类疟疾载体冈比亚按蚊的男性偏见性别扭曲基因驱动。

只有雌性昆虫会传播疟疾、登革热和寨卡病毒等疾病；因此，长期以来一直在寻找偏向昆虫后代性别比例的控制方法。性染色体驱动等遗传因素可以扭曲性别比例，从而产生最终崩溃的男女通用种群，但潜在的分子机制尚不清楚。我们报告了人类疟疾载体冈比亚按蚊中的男性偏见性别扭曲基因驱动 (SDGD)。我们通过将 X 染色体切碎 I-PpoI 核酸酶与插入双性 (dsx) 基因保守序列中的基于 CRISPR 的基因驱动耦合来诱导 X 染色体切碎 I-PpoI 核酸酶的超孟德尔遗传。在入侵动力学建模中，与以前开发的针对雌性生育能力的基因驱动相比，预测 SDGD 对雌性蚊子种群的影响更快。dsx 基因座上的 SDGD 在 10-14 代中从 2.5% 的起始等位基因频率导致只有男性的种群，种群崩溃并且没有抗性选择。我们的结果支持使用 SDGD 控制疟疾病媒。