A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias

Sebald A. N. Verkuijl, Estela Gonzalez, Ming Li, Joshua X. D. Ang, Nikolay P. Kandul, Michelle A. E. Anderson, Omar S. Akbari, Michael B. Bonsall and Luke Alphey ()
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Sebald A. N. Verkuijl: University of Oxford
Estela Gonzalez: The Pirbright Institute
Ming Li: University of California San Diego
Joshua X. D. Ang: The Pirbright Institute
Nikolay P. Kandul: University of California San Diego
Michelle A. E. Anderson: The Pirbright Institute
Omar S. Akbari: University of California San Diego
Michael B. Bonsall: University of Oxford
Luke Alphey: The Pirbright Institute

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract CRISPR/Cas gene drives can bias transgene inheritance through different mechanisms. Homing drives are designed to replace a wild-type allele with a copy of a drive element on the homologous chromosome. In Aedes aegypti, the sex-determining locus is closely linked to the white gene, which was previously used as a target for a homing drive element (wGDe). Here, through an analysis using this linkage we show that in males inheritance bias of wGDe did not occur by homing, rather through increased propagation of the donor drive element. We test the same wGDe drive element with transgenes expressing Cas9 with germline regulatory elements sds3, bgcn, and nup50. We only find inheritance bias through homing, even with the identical nup50-Cas9 transgene. We propose that DNA repair outcomes may be more context dependent than anticipated and that other previously reported homing drives may, in fact, bias their inheritance through other mechanisms.

Date: 2022
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DOI: 10.1038/s41467-022-34739-y

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