Abstract
Scientists are rapidly developing synthetic gene drive elements intended for release into natural populations. These are intended to control or eradicate disease vectors and pests, or to spread useful traits through wild populations for disease control or conservation purposes. However, a crucial problem for gene drives is the evolution of resistance against them, preventing their spread. Understanding the mechanisms by which populations might evolve resistance is essential for engineering effective gene drive systems. This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in general.
Highlights
KEYWORDS CRISPR-Cas9, fitness costs, meiotic drive, population suppression, selfish genetic elements, sex ratio distorter, transposable element, Wolbachia
Does resistance usually arise through selection on pre-existing genetic variation, or does it more often involve novel mutations that appear once drive has reached a high frequency? What fraction of natural gene drives reach fixation, go extinct, reach a stable polymorphism or are fully suppressed, and how can we address this question given the difficulties of detection once a gene drive has fixed or been lost? Does resistance to drive typically involve the same fundamental mechanism across species and types of drivers, or is the resistance mechanism highly idiosyncratic?
It is a major challenge faced by natural gene drive systems but remains poorly understood
Summary
KEYWORDS CRISPR-Cas9, fitness costs, meiotic drive, population suppression, selfish genetic elements, sex ratio distorter, transposable element, Wolbachia This research suggests that we should expect synthetic gene drives, especially those with large fitness effects, to select for resistance, which will potentially undermine their ability to spread, and modify or suppress populations (Barrett et al, 2019; Holman, 2019; Unckless et al, 2017). Female drivers might readily spread and fix, since only a small region of the genome close to the drive locus would be under selection to evolve resistance.
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