School of Mathematical Sciences, The University of Adelaide, Adelaide, Australia.
School of Medicine, The University of Adelaide, Adelaide, Australia.
Elife. 2019 Feb 15;8:e41873. doi: 10.7554/eLife.41873.
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 (. 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.
自我复制的基因驱动，通过改变性别比例或推断出适应度成本，可以用于控制入侵外来物种的种群。使用 CRISPR 技术靶向删除 Y 性染色体为性偏见提供了一种新方法，可以将其纳入基因驱动设计中。我们引入了一种新的基因驱动策略，称为使用正交可编程内切酶的 Y 染色体缺失（Y-CHromosome deletion using Orthogonal Programmable Endonucleases，Y-CHOPE），该策略结合了一种可编程内切酶，可以“粉碎”Y 染色体，从而将 XY 雄性转变为可育的 XO 雌性。首先，我们证明 CRISPR/Cas12a 系统可以高效率地（>.90%）消除胚胎干细胞中的 Y 染色体。接下来，使用害虫小鼠种群的随机个体基础模型，我们表明，通过限制交配，逐渐耗尽 XY 雄性群体的 Y 染色体粉碎驱动可能会通过限制交配来实现种群灭绝。我们的分子和建模数据表明，Y-CHOPE 基因驱动可能是一种可行的控制脊椎动物害虫的工具。
