Phylogenetic and toxicogenomic profiling of CYPomes to elucidate convergent and divergent insecticide resistance profiles in three rice planthopper species

Insecticide resistance in pest control poses a threat to agricultural production and human health. Numerous insect species express genes coding for detoxification enzymes that have broad substrate promiscuity thus conferring resistance to various insecticides. However, whether the homologs of these genes play similar roles in resistance phenotypes of closely related species remains largely unclear. Therefore, this study compares the resistance profiles of three major rice planthopper species (Delphacidae) (Laodelphax striatellus, Nilaparvata lugens, and Sogatella furcifera) based on the metabolic activity of their cytochrome P450s. Genome-wide analyses resulted in 68, 70, and 64 P450 genes in L. striatellus, N. lugens, and S. furcifera, respectively. Phylogenetic analyses among these genes found that most resistance-related genes in one species had homologs in other planthopper species. The most resistance-relevant orthogroup (CYP6ERs) showed higher evolutionary instability than most other groups. RNAi and in vitro metabolism assays revealed that CYP6ERs confers more divergent insecticide resistance profiles among planthopper species than the other two major resistance-related P450 subfamilies (CYP6AYs and CYP4C61s). Alphafold-based structural predictions and alignments suggested that P450 orthogroups with higher phylogenetic instability tended to have less structural similarities, resulting in more divergent metabolic profiles. This relationship was also in silico validated on Aphidae aphids and Lepidoptera noctuids. This study proposes combined phylogenetic and toxicogenomic analyses for understanding CYPome-based insecticide resistance convergency and divergency among closely related pests. These findings may improve the accuracy and rationality of chemical pest control.