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

Nat Biotechnol. 2020 Sep;38(9):1054-1060. doi: 10.1038/s41587-020-0508-1. Epub 2020 May 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anopheles / genetics*
  • CRISPR-Associated Protein 9 / genetics
  • CRISPR-Associated Protein 9 / metabolism
  • CRISPR-Cas Systems / genetics
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism
  • Female
  • Gene Drive Technology / methods*
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • Malaria / prevention & control
  • Malaria / transmission*
  • Male
  • Mosquito Control
  • Mosquito Vectors / genetics*
  • Sex Determination Processes / genetics*
  • X Chromosome / genetics
  • X Chromosome / metabolism

Substances

  • Insect Proteins
  • CRISPR-Associated Protein 9
  • Endodeoxyribonucleases
  • I-Ppo endonuclease