The molecular mechanisms of coevolution between plants and insects remain elusive. GABA receptors are targets of many neurotoxic terpenoids, which represent the most diverse array of natural products known. Over deep evolutionary time, as plant terpene synthases diversified in plants, so did plant terpenoid defence repertoires. Here we show that herbivorous insects and their predators evolved convergent amino acid changing substitutions in duplicated copies of the Resistance to dieldrin (Rdl) gene that encodes the GABA receptor, and that the evolution of duplicated Rdl and terpenoid-resistant GABA receptors is associated with the diversification of moths and butterflies. These same substitutions also evolved in pests exposed to synthetic insecticides that target the GABA receptor. We used in vivo genome editing in Drosophila melanogaster to evaluate the fitness effects of each putative resistance mutation and found that pleiotropy both facilitates and constrains the evolution of GABA receptor resistance. The same genetic changes that confer resistance to terpenoids across 300 Myr of insect evolution have re-evolved in response to synthetic analogues over one human lifespan.

植物和昆虫之间共同进化的分子机制仍然难以捉摸。 GABA 受体是许多神经毒性萜类化合物的靶标，这些萜类化合物代表了已知最多样化的天然产物。在漫长的进化过程中，随着植物萜烯合酶的多样化，植物萜类化合物的防御能力也随之多样化。在这里，我们表明，草食性昆虫及其捕食者在编码 GABA 受体的抗狄氏剂( Rdl ) 基因的重复拷贝中进化出趋同的氨基酸改变取代，并且重复的Rdl和萜类化合物抗性 GABA 受体的进化与飞蛾和蝴蝶的多样化。这些相同的替代也在暴露于针对 GABA 受体的合成杀虫剂的害虫中进化。我们使用果蝇体内基因组编辑来评估每个假定的抗性突变的适应性效果，发现多效性既促进又限制 GABA 受体抗性的进化。在昆虫进化 300 密尔的过程中，赋予萜类化合物抗性的相同基因变化，在人类的一生中，为了响应合成类似物而重新进化。