Cytochrome P450 drives divergent adaptation to quercetin in invasive and native fruit borers

The coevolutionary arms race between plants and herbivores is a key driver of insect adaptation. While the global invasive fruit borer Cydia pomonella shows slower adaptation to the plant secondary metabolite quercetin compared to native species Grapholita molesta, the molecular basis remains unclear. Here, we clarify the divergent evolutionary mechanisms governing the adaptation of these two species to quercetin. Results revealed enhanced quercetin metabolic capacity in adapted populations of both species relative to their non-adapted counterparts. G. molesta relies on the canonical detoxification-associated P450 genes CYP6AB364 and CYP341Q10 belonging to the CYP3 and CYP4 clans, respectively, showing positive correlation with adaptation. In contrast, C. pomonella employs a member of the CYP3 clan (CYP337B19) and specific mitochondrial P450 genes (CYP333B119 and CYP333B118). Artificial intelligence (AI)-based molecular docking assay confirmed strong binding interactions between these P450 enzymes and quercetin. Knockdown of these genes reduced metabolic adaptation, and in vitro assays showed decreased metabolic efficiency post-silencing. Notably, recombinant P450 enzymes from C. pomonella (with the exception of CYP337B19) exhibited lower quercetin metabolic capability than G. molesta's. These findings suggest divergent adaptive strategies between species, with the invasive C. pomonella potentially employing neofunctionalized mitochondrial P450s for quercetin detoxification and facilitate adaption. G. molesta's superior quercetin metabolism likely drives its greater adaptability, advancing our understanding of host adaptation and interspecific interactions in pest species.