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Invasion and migration of spatially self‐limiting gene drives: A comparative analysis

机译:空间自限性基因驱动器的入侵和迁移:比较分析

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摘要

Recent advances in research on gene drives have produced genetic constructs that could theoretically spread a desired gene (payload) into all populations of a species, with a single release in one place. This attribute has advantages, but also comes with risks and ethical concerns. There has been a call for research on gene drive systems that are spatially and/or temporally self‐limiting. Here, we use a population genetics model to compare the expected characteristics of three spatially self‐limiting gene drive systems: one‐locus underdominance, two‐locus underdominance and daisy‐chain drives. We find large differences between these gene drives in the minimum release size required for successfully driving a payload into a population. The daisy‐chain system is the most efficient, requiring the smallest release, followed by the two‐locus underdominance system, and then the one‐locus underdominance system. However, when the target population exchanges migrants with a nontarget population, the gene drives requiring smaller releases suffer from higher risks of unintended spread. For payloads that incur relatively low fitness costs (up to 30%), a simple daisy‐chain drive is practically incapable of remaining localized, even with migration rates as low as 0.5% per generation. The two‐locus underdominance system can achieve localized spread under a broader range of migration rates and of payload fitness costs, while the one‐locus underdominance system largely remains localized. We also find differences in the extent of population alteration and in the permanence of the alteration achieved by the three gene drives. The two‐locus underdominance system does not always spread the payload to fixation, even after successful drive, while the daisy‐chain system can, for a small set of parameter values, achieve a temporally limited spread of the payload. These differences could affect the suitability of each gene drive for specific applications.
机译:基因驱动研究的最新进展已经产生了遗传构建物,该构建物理论上可以将所需基因(有效载荷)传播到一个物种的所有种群中,并且一次释放一次。此属性具有优势,但同时也带有风险和道德方面的顾虑。已经呼吁研究在空间和/或时间上自限的基因驱动系统。在这里,我们使用种群遗传学模型来比较三种空间自限基因驱动系统的预期特征:单基因座不足,两基因座不足和菊花链驱动。我们发现这些基因驱动器之间的巨大差异在于成功将有效负载驱动到种群所需的最小释放大小。菊链系统是最有效的,需要最小的释放,其次是两位置不足主导系统,然后是单位置不足主导系统。但是,当目标人群与非目标人群交换移民时,需要较小释放量的基因驱动器会遭受意想不到的传播的更高风险。对于适应性成本相对较低(高达30%)的有效载荷,即使每代迁移率低至0.5%,简单的菊花链驱动器实际上也无法保持本地化。两地点不足主导系统可以在更大范围的迁移率和有效载荷适应性成本下实现局部扩散,而一地点不足主导系统在很大程度上仍保持本地化。我们还发现了人口变化的程度以及这三个基因驱动所实现的变化的持久性方面的差异。即使在成功驱动之后,双位元不足控制系统也不会始终将有效载荷散布到注视点上,而菊花链系统可以通过少量参数值实现在时间上有限的有效载荷散布。这些差异可能会影响每个基因驱动器对特定应用的适用性。

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