Cleave and Rescue gamete killers create conditions for gene drive in plants

Gene drive elements promote the spread of linked traits, even when their presence confers a fitness cost to carriers, and can be used to change the composition or fate of wild populations. Cleave and Rescue (ClvR) drive elements sit at a fixed chromosomal position and include a DNA sequence-modifying enzyme such as Cas9/gRNAs (the Cleaver/Toxin) that disrupts endogenous versions of an essential gene, and a recoded version of the essential gene resistant to cleavage (the Rescue/Antidote). ClvR spreads by creating conditions in which those lacking ClvR die because they lack functional versions of the essential gene. We demonstrate the essential features of ClvR gene drive in the plant Arabidopsis thaliana through killing of gametes that fail to inherit a ClvR that targets the essential gene YKT61, whose expression is required in male and female gametes for their survival. Resistant (uncleavable but functional) alleles, which can slow or prevent drive, were not observed. Modeling shows plant ClvRs can be used to rapidly drive population modification or suppression. Possible applications in weed control, plant breeding and conservation are discussed.

基因驱动（Gene drive）元件可促进连锁性状的扩散，即便其存在会给携带个体带来适合度代价，同时可用于改变野生种群的组成与存续命运。剪切-救援（Cleave and Rescue, ClvR）型基因驱动元件固定位于染色体特定位置，包含一类DNA序列修饰酶（如Cas9/gRNAs，即剪切因子/毒素），可破坏必需基因的内源拷贝；同时还携带经重编码的该必需基因版本，该版本可抵御剪切（即救援因子/解毒剂）。ClvR通过构建如下条件实现扩散：缺少ClvR的个体因缺乏该必需基因的功能拷贝而死亡。本研究在模式植物拟南芥（Arabidopsis thaliana）中验证了ClvR基因驱动的核心特征：通过使未继承靶向必需基因YKT61的ClvR的配子死亡，YKT61的表达对雌雄配子的存活均为必需。本研究未观测到可减缓或阻断驱动过程的抗性（未被剪切但功能正常）等位基因。模型模拟结果表明，植物源ClvR可用于快速实现种群改造或种群抑制。本文讨论了其在杂草防控、植物育种及物种保护中的潜在应用。