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

Thomas Aa Prowse, Fatwa Adikusuma, Phillip Cassey, Paul Thomas, Joshua V. Ross

Research output: Contribution to journalArticle

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.

LanguageEnglish
JournaleLife
Volume8
DOIs
Publication statusPublished - 15 Feb 2019

Keywords

  • CRISPR
  • computational biology
  • gene drive
  • genetics
  • genomics
  • island conservation
  • mouse
  • pest control
  • resistance allele
  • sex-ratio distortion
  • systems biology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

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title = "A Y-chromosome shredding gene drive for controlling pest vertebrate populations",
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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A Y-chromosome shredding gene drive for controlling pest vertebrate populations. / Prowse, Thomas Aa; Adikusuma, Fatwa; Cassey, Phillip; Thomas, Paul; Ross, Joshua V.

In: eLife, Vol. 8, 15.02.2019.

Research output: Contribution to journalArticle

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AU - Adikusuma, Fatwa

AU - Cassey, Phillip

AU - Thomas, Paul

AU - Ross, Joshua V.

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