A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias

TY - JOUR

T1 - A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias

AU - Verkuijl, Sebald

AU - Gonzalez Fernandez, Estela

AU - Li, Ming

AU - Ang Xin De, Joshua

AU - Kandul, Nikolay

AU - Anderson, Michelle

AU - Akbari, Omar

AU - Bonsall, Michael

AU - Alphey, Luke Stephen

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022/11/21

Y1 - 2022/11/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85142365280&partnerID=8YFLogxK

U2 - 10.1101/2020.12.15.421271

DO - 10.1101/2020.12.15.421271

M3 - Article

C2 - 36414618

AN - SCOPUS:85142365280

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7145

ER -