Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125
Proc Natl Acad Sci U S A. 2021 Dec 7;118(49). doi: 10.1073/pnas.2107413118.
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. () selfish genetic elements use Cas9 and guide RNAs (gRNAs) to disrupt endogenous versions of an essential gene while also including a version of the essential gene resistant to disruption. spreads by creating loss-of-function alleles of the essential gene that select against those lacking it, resulting in populations in which the provides the only source of essential gene function. As a consequence, if function of the , 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 in in which activity of an essential gene, , requires splicing of a temperature-sensitive intein (TS- ). This element spreads to transgene fixation at 23 °C, but when populations now dependent on Ts- 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 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.
一种种群抑制策略是利用基因驱动来传播赋予条件致死或不育的基因,从而将种群修饰与抑制结合起来。潜在感兴趣的刺激物可以由人类引入,例如良性病毒或化学物质,或者自然地按季节性发生,例如温度变化。 ()自私的遗传元件使用 Cas9 和向导 RNA(gRNA)来破坏必需基因的内源性版本,同时还包括对破坏具有抗性的必需基因的版本。通过创建必需基因的失活等位基因来传播,这些等位基因对缺乏该基因的基因具有选择作用,导致种群中只有必需基因的功能。因此,如果 (一种无处不在的特洛伊木马)的功能是条件依赖性的,那么该种群的生存也是如此。为了验证这一想法,我们在 中创建了一个 ,其中必需基因的 活性需要温度敏感整合酶(TS-)的剪接。该元件在 23°C 时传播到转基因固定,但当现在依赖 Ts-的种群转移到 29°C 时,死亡和不育会导致种群迅速崩溃。这些结果表明可以实现条件性种群消除。基于同源的驱动和响应其他刺激物对特定个体进行抑制和/或杀伤的类似逻辑,也可以使用条件性 活性。