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

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dc.contributor.authorProwse, T.A.
dc.contributor.authorAdikusuma, F.
dc.contributor.authorCassey, P.
dc.contributor.authorThomas, P.
dc.contributor.authorRoss, J.V.
dc.date.issued2019
dc.description.abstractSelf-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.
dc.description.statementofresponsibilityThomas AA Prowse, Fatwa Adikusuma, Phillip Cassey, Paul Thomas, Joshua V Ross
dc.identifier.citationeLife, 2019; 8:e41873-1-e41873-19
dc.identifier.doi10.7554/eLife.41873
dc.identifier.issn2050-084X
dc.identifier.issn2050-084X
dc.identifier.orcidProwse, T.A. [0000-0002-4093-767X]
dc.identifier.orcidAdikusuma, F. [0000-0003-2163-0514]
dc.identifier.orcidCassey, P. [0000-0002-2626-0172]
dc.identifier.orcidRoss, J.V. [0000-0002-9918-8167]
dc.identifier.urihttp://hdl.handle.net/2440/129007
dc.language.isoen
dc.publishereLife
dc.rightsCopyright 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.
dc.source.urihttps://doi.org/10.7554/elife.41873
dc.subjectCRISPR
dc.subjectcomputational biology
dc.subjectgene drive
dc.subjectgenetics
dc.subjectgenomics
dc.subjectisland conservation
dc.subjectmouse
dc.subjectpest control
dc.subjectresistance allele
dc.subjectsex-ratio distortion
dc.subjectsystems biology
dc.titleA Y-chromosome shredding gene drive for controlling pest vertebrate populations
dc.typeJournal article
pubs.publication-statusPublished

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