School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;
Kavli Institute for Bionano Science and Technology, Harvard University, Cambridge, MA 02138.
Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):8452-8457. doi: 10.1073/pnas.1705868114. Epub 2017 Jul 25.
Gene drives have the potential to rapidly replace a harmful wild-type allele with a gene drive allele engineered to have desired functionalities. However, an accidental or premature release of a gene drive construct to the natural environment could damage an ecosystem irreversibly. Thus, it is important to understand the spatiotemporal consequences of the super-Mendelian population genetics before potential applications. Here, we use a reaction-diffusion model for sexually reproducing diploid organisms to study how a locally introduced gene drive allele spreads to replace the wild-type allele, although it possesses a selective disadvantage > 0. Using methods developed by Barton and collaborators, we show that socially responsible gene drives require 0.5 < < 0.697, a rather narrow range. In this "pushed wave" regime, the spatial spreading of gene drives will be initiated only when the initial frequency distribution is above a threshold profile called "critical propagule," which acts as a safeguard against accidental release. We also study how the spatial spread of the pushed wave can be stopped by making gene drives uniquely vulnerable ("sensitizing drive") in a way that is harmless for a wild-type allele. Finally, we show that appropriately sensitized drives in two dimensions can be stopped, even by imperfect barriers perforated by a series of gaps.
基因驱动有潜力快速将有害的野生型等位基因替换为经过设计具有所需功能的基因驱动等位基因。然而,基因驱动构建体意外或过早释放到自然环境中可能会对生态系统造成不可逆转的破坏。因此,在潜在应用之前,了解超孟德尔种群遗传学的时空后果非常重要。在这里,我们使用反应扩散模型来研究性繁殖二倍体生物,研究局部引入的基因驱动等位基因如何传播以取代野生型等位基因,尽管它具有选择劣势 > 0。使用 Barton 及其合作者开发的方法,我们表明,负责任的基因驱动需要 0.5 < < 0.697,范围相当窄。在这种“推动波”模式下,只有当初始频率分布高于称为“临界传播体”的阈值分布时,基因驱动的空间传播才会启动,这可以作为防止意外释放的一种保护措施。我们还研究了如何通过使基因驱动在某种程度上变得独特脆弱(“敏感驱动”)而停止推动波的空间传播,这种方式对野生型等位基因是无害的。最后,我们表明,在二维空间中,适当的敏感驱动甚至可以通过一系列间隙穿孔的不完美屏障来停止。