Program for Evolutionary Dynamics, Harvard University, Cambridge, United States.
Department of Genetics, Harvard Medical School, Harvard University, Boston, United States.
Elife. 2018 Jun 19;7:e33423. doi: 10.7554/eLife.33423.
Recent reports have suggested that self-propagating CRISPR-based gene drive systems are unlikely to efficiently invade wild populations due to drive-resistant alleles that prevent cutting. Here we develop mathematical models based on existing empirical data to explicitly test this assumption for population alteration drives. Our models show that although resistance prevents spread to fixation in large populations, even the least effective drive systems reported to date are likely to be highly invasive. Releasing a small number of organisms will often cause invasion of the local population, followed by invasion of additional populations connected by very low rates of gene flow. Hence, initiating contained field trials as tentatively endorsed by the National Academies report on gene drive could potentially result in unintended spread to additional populations. Our mathematical results suggest that self-propagating gene drive is best suited to applications such as malaria prevention that seek to affect all wild populations of the target species.
最近的报告表明，由于能够阻止切割的抗性等位基因，自我传播的基于 CRISPR 的基因驱动系统不太可能有效地入侵野生种群。在这里，我们基于现有经验数据开发了数学模型，以明确测试该假设对种群改变驱动的适用性。我们的模型表明，尽管抗性会阻止在大种群中传播到固定状态，但即使是迄今为止报道的最无效的驱动系统，也可能具有很强的入侵性。释放少量的生物体通常会导致当地种群的入侵，然后是通过极低基因流率连接的其他种群的入侵。因此，正如国家科学院关于基因驱动的报告中暂定批准的那样，启动有控制的田间试验可能会导致意外传播到其他种群。我们的数学结果表明，自我传播的基因驱动最适合于预防疟疾等应用，这些应用旨在影响目标物种的所有野生种群。
