Oberhofer Georg, Johnson Michelle L, Ivy Tobin, Antoshechkin Igor, Hay Bruce A
California Institute of Technology. Division of Biology and Biological Engineering. 1200 East California Boulevard, MC156-29, Pasadena, CA 91125.
bioRxiv. 2024 Feb 27:2023.10.13.562303. doi: 10.1101/2023.10.13.562303.
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 () 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). spreads by creating conditions in which those lacking die because they lack functional versions of the essential gene. We demonstrate the essential features of gene drive in the plant through killing of gametes that fail to inherit a 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 s are likely to be robust to certain failure modes and can be used to rapidly drive population modification or suppression. Possible applications in plant breeding, weed control, and conservation are discussed.
基因驱动元件促进连锁性状的传播,即使它们的存在会给携带者带来适应性代价,并且可用于改变野生种群的组成或命运。切割与拯救(Cleave and Rescue,CaR)驱动元件位于固定的染色体位置,包括一种DNA序列修饰酶,如Cas9/gRNAs(切割器/毒素),它会破坏一个必需基因的内源版本,以及该必需基因的一个对切割具有抗性的重新编码版本(拯救者/解毒剂)。CaR通过创造一种条件来传播,即那些缺乏CaR的个体因缺乏必需基因的功能版本而死亡。我们通过杀死未能继承靶向必需基因YKT61的CaR的配子,在植物拟南芥中展示了CaR基因驱动的基本特征,YKT61的表达在雄配子和雌配子存活中是必需的。未观察到可减缓或阻止驱动的抗性(不可切割但有功能的)等位基因。模型显示,植物CaR可能对某些失败模式具有鲁棒性,并且可用于快速推动种群修饰或抑制。文中还讨论了其在植物育种、杂草控制和保护方面的可能应用。