Gene drive that results in addiction to a temperature-sensitive version of an essential gene triggers population collapse in <i>Drosophila</i>.

Abstract

One strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise benign virus or chemical, or occur naturally on a seasonal basis, such as a change in temperature. <i>Cleave and Rescue</i> (<i>ClvR</i>) selfish genetic elements use Cas9 and guide RNAs (gRNAs) to disrupt endogenous versions of an essential gene while also including a <i>Rescue</i> version of the essential gene resistant to disruption. <i>ClvR</i> spreads by creating loss-of-function alleles of the essential gene that select against those lacking it, resulting in populations in which the <i>Rescue</i> provides the only source of essential gene function. As a consequence, if function of the <i>Rescue</i>, a kind of Trojan horse now omnipresent in a population, is condition dependent, so too will be the survival of that population. To test this idea, we created a <i>ClvR</i> in <i>Drosophila</i> in which <i>Rescue</i> activity of an essential gene, <i>dribble</i>, requires splicing of a temperature-sensitive intein (TS-<i>ClvR^dbe</i> ). This element spreads to transgene fixation at 23 °C, but when populations now dependent on Ts-<i>ClvR^db</i>^e are shifted to 29 °C, death and sterility result in a rapid population crash. These results show that conditional population elimination can be achieved. A similar logic, in which <i>Rescue</i> activity is conditional, could also be used in homing-based drive and to bring about suppression and/or killing of specific individuals in response to other stimuli.