Abundance of conserved CRISPR-Cas9 target sites within the highly polymorphic genomes of Anopheles and Aedes mosquitoes

H. Schmidt, T. C. Collier, M. J. Hanemaaijer, P. D. Houston, Y. Lee and G. C. Lanzaro,  Nature Communications,  11. 2020.

A number of recent papers report that standing genetic variation in natural populations includes ubiquitous polymorphisms within target sites for Cas9-based gene drive (CGD) and that these “drive resistant alleles” (DRA) preclude the successful application of CGD for managing these populations. Here we report the results of a survey of 1280 genomes of the mosquitoes Anopheles gambiae, An. coluzzii, and Aedes aegypti in which we determine that similar to 90% of all protein-encoding CGD target genes in natural populations include at least one target site with no DRAs at a frequency of >= 1.0%. We conclude that the abundance of conserved target sites in mosquito genomes and the inherent flexibility in CGD design obviates the concern that DRAs present in the standing genetic variation of mosquito populations will be detrimental to the deployment of this technology for population modification strategies. Genetic variation in natural populations could represent gene drive resistant alleles, preventing successful application for population management. Here the authors survey 1280 genomes from three mosquito species and concludes natural variation will not be detrimental to deploying gene drive technology.

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