CYP9A P450 clusters in lepidopterans contribute to host plant adaptation and insecticide resistance

What is it about?

Here we provide mechanistic support for the involvement of the CYP9A subfamily of cytochrome P450s in the detoxification of host plant defense compounds and chemical insecticides in Spodoptera exigua and Spodoptera frugiperda. Our comparative genomics shows that a large cluster of CYP9A genes occurs in the two species but with significant differences in its contents, including several species-specific duplicates and substantial sequence divergence, both between orthologs and between duplicates. Bioassays of CRISPR-Cas9 knockouts of the clusters show that, collectively, the CYP9As can detoxify two furanocoumarin plant defense compounds (imperatorin and xanthotoxin) and insecticides representing three different chemotypes (pyrethroids, avermectins and oxadiazines). However, in vitro metabolic assays of heterologously expressed products of individual genes show several differences between the species in the particular CYP9As with activities against these compounds. We also find that the clusters show tight genetic linkage with high levels of pyrethroid resistance in field strains of the two species. We propose that their divergent amplifications of the CYP9A subfamily have not only contributed to the development of the broad host ranges of these species over long evolutionary timeframes but also supplied them with diverse genetic options for evolving resistance to chemical insecticides in the very recent past.

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Why is it important?

We provide mechanistic evidence linking a cluster of rapidly diverging cytochrome P450 genes in two insect pests to their ability to utilise diverse host plants and their propensity to evolve insecticide resistance. CRISPR-Cas9 technology, bioassays and biochemical assays show that amplified CYP9As in Spodoptera exigua and Spodoptera frugiperda collectively metabolize furanocoumarin plant defense compounds and pyrethroid, avermectin and oxadiazine insecticides but with many differences between the species in the particular CYP9As with activity against these compounds. We also show pyrethroid resistance in both species co-segregates with the amplified gene cluster in genetic crosses. We suggest the cluster has contributed to both the long-term macroevolution of these polyphagous insects to diverse hosts and pre-adapted them for short-term microevolution of insecticide resistance.