Catch Me If You Can: A Spatial Model for a Brake-Driven Gene Drive Reversal
Catch Me If You Can: A Spatial Model for a Brake-Driven Gene Drive Reversal
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DOI：
10.1007/s11538-019-00668-z
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发表时间：
2019-10-12
影响因子：
3.5
通讯作者：
Debarre, Florence
中科院分区：
文献类型：
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作者：
Girardin, Leo;Calvez, Vincent;Debarre, Florence
随着CRISPR-Cas基因工程技术的发展，利用人工基因驱动（等位基因偏遗传，增加自身传递给后代）进行种群管理正成为一种现实的可能性。然而，基因驱动可能不得不停止。有人提出了“解药”（刹车），但迄今为止只在混合良好的人群中进行了研究。在这里，我们考虑一个反应-扩散系统，模拟一个基因驱动（适应度为1-a\）在野生型种群（适应度为1）中的释放。证明了当驱动适应度不超过1/2，而制动适应度接近1时，从长期来看，制动与驱动发生共消。相反，如果驱动适应度大于1/2，则不可能共灭绝，驱动和制动在空间上持续扩散，在入侵尾流中留下复杂的时空异质性遗传模式。基于数值实验，我们支持全局共消猜想，假设驱动适应度最多为1/2，而不考虑制动适应度。这一证据依赖于对一个对猎物具有强Allee效应的捕食者-猎物系统的研究。我们的研究结果表明，有些驱动可能是不可阻挡的，如果基因驱动在自然界中被部署，那么只有在足够高的频率下才会传播的阈值驱动应该是首选。
Population management using artificial gene drives (alleles biasing inheritance, increasing their own transmission to offspring) is becoming a realistic possibility with the development of CRISPR-Cas genetic engineering. A gene drive may, however, have to be stopped. "Antidotes" (brakes) have been suggested, but have been so far only studied in well-mixed populations. Here, we consider a reaction-diffusion system modeling the release of a gene drive (of fitness 1-a\) in a wild-type population (fitness 1). We prove that whenever the drive fitness is at most 1/2 while the brake fitness is close to 1, coextinction of the brake and the drive occurs in the long run. On the contrary, if the drive fitness is greater than 1/2, then coextinction is impossible: the drive and the brake keep spreading spatially, leaving in the invasion wake a complicated spatiotemporally heterogeneous genetic pattern. Based on numerical experiments, we argue in favor of a global coextinction conjecture provided the drive fitness is at most 1/2, irrespective of the brake fitness. The proof relies upon the study of a related predator-prey system with strong Allee effect on the prey. Our results indicate that some drives may be unstoppable and that if gene drives are ever deployed in nature, threshold drives, that only spread if introduced in high enough frequencies, should be preferred.