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

Simoni, Alekos; Hammond, Andrew M.; Beaghton, Andrea K.; Galizi, Roberto; Taxiarchi, Chrysanthi; Kyrou, Kyros; Meacci, Dario; Gribble, Matthew; Morselli, Giulia; Burt, Austin; Nolan, Tony; Crisanti, Andrea

doi:10.1038/s41587-020-0508-1

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

Simoni, Alekos; Hammond, Andrew M.; Beaghton, Andrea K.; Galizi, Roberto; Taxiarchi, Chrysanthi; Kyrou, Kyros; Meacci, Dario; Gribble, Matthew; Morselli, Giulia; Burt, Austin; Nolan, Tony; Crisanti, Andrea

Authors

Alekos Simoni

Andrew M. Hammond

Andrea K. Beaghton

Roberto Galizi r.galizi@keele.ac.uk

Chrysanthi Taxiarchi

Kyros Kyrou

Dario Meacci

Matthew Gribble

Giulia Morselli

Austin Burt

Tony Nolan

Andrea Crisanti

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.

Journal Article Type	Article
Acceptance Date	Apr 1, 2020
Publication Date	2020
Publicly Available Date	May 26, 2023
Journal	Nature Biotechnology
Print ISSN	1087-0156
Publisher	Nature Publishing Group
ISBN	15461696 10870156
DOI	https://doi.org/10.1038/s41587-020-0508-1
Keywords	Gene regulation; Genetics; Molecular engineering
Publisher URL	https://doi.org/10.1038/s41587-020-0508-1