A Y-chromosome shredding gene drive for controlling pest vertebrate populations

Date

2019

Authors

Prowse, T.A.
Adikusuma, F.
Cassey, P.
Thomas, P.
Ross, J.V.

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Journal article

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eLife, 2019; 8:e41873-1-e41873-19

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Thomas AA Prowse, Fatwa Adikusuma, Phillip Cassey, Paul Thomas, Joshua V Ross

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Abstract

Self-replicating gene drives that modify sex ratios or infer a fitness cost could be used to control populations of invasive alien species. The targeted deletion of Y sex chromosomes using CRISPR technology offers a new approach for sex bias that could be incorporated within gene-drive designs. We introduce a novel gene-drive strategy termed Y-CHromosome deletion using Orthogonal Programmable Endonucleases (Y-CHOPE), incorporating a programmable endonuclease that 'shreds' the Y chromosome, thereby converting XY males into fertile XO females. Firstly, we demonstrate that the CRISPR/Cas12a system can eliminate the Y chromosome in embryonic stem cells with high efficiency (c. 90%). Next, using stochastic, individual-based models of a pest mouse population, we show that a Y-shredding drive that progressively depletes the pool of XY males could effect population eradication through mate limitation. Our molecular and modeling data suggest that a Y-CHOPE gene drive could be a viable tool for vertebrate pest control.

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Copyright Prowse et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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