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

TLDR

Only female insects transmit diseases such as malaria, dengue and Zika, so methods that bias the sex ratio of insect offspring have long been sought. The authors engineered a super‑Mendelian X‑chromosome‑shredding I‑PpoI nuclease linked to a CRISPR gene drive inserted into a conserved region of the doublesex gene. Modeling and experiments show that the SDGD rapidly drives a male‑only population from a 2.5 % allele frequency within 10–14 generations, collapsing the population without resistance, supporting its use for malaria vector control.

Abstract

Abstract 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.