A CRISPR endonuclease gene drive reveals distinct mechanisms of inheritance bias
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 21, 2022
- Source ID
- 10.1038/s41467-022-34739-y
Entities
People
- Estela González
- Joshua X D Ang
- Luke Alphey
- Michael B. Bonsall
- Michelle A E Anderson
- Ming Li
- Nikolay P. Kandul
- Omar S. Akbari
- Sebald A. N. Verkuijl
Organizations
- Biotechnology and Biological Sciences Research Council
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- United States Department of Defense
- United States Department of Health and Human Services