A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias

Sebald Verkuijl, Estela Gonzalez Fernandez, Ming Li, Joshua Ang Xin De, Nikolay Kandul, Michelle Anderson, Omar Akbari, Michael Bonsall, Luke Stephen Alphey*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number7145
Number of pages10
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 21 Nov 2022

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