The genetic architecture of resistance to flubendiamide insecticides inHelicoverpa armigera(Hübner) (Lepidoptera: Noctuidae)

Insecticide resistance is a major problem in food production, environmental sustainability, and human health. The cotton bollworm Helicoverpa armigera is a globally distributed crop pest affecting over 300 crop species. H. armigera has rapidly evolved insecticide resistance, making it one of the most damaging pests worldwide. Understanding the genetic basis of insecticide resistance provides insights to develop tools, such as molecular markers, that can be used to slow or prevent the evolution of resistance. We explore the genetic architecture of H. armigera resistance to a widely used insecticide, flubendiamide, using two complementary approaches: genome-wide association studies (GWAS) in wild-caught samples and quantitative trait locus (QTL) mapping in a controlled cross of susceptible and resistant laboratory strains. Both approaches identified one locus on chromosome 2, revealing two SNPs within 976 bp that can be used to monitor field resistance to flubendiamide. This was the only region identified using linkage mapping, though GWAS revealed additional sites associated with resistance. Other loci identified by GWAS in field populations contained known insecticide detoxification genes from the ATP-binding cassette family, ABCA1, ABCA3, ABCF2 and MDR1. Our findings revealed an oligogenic genetic architecture, in contrast to previous reports of monogenic resistance associated with the ryanodine receptor . This work elucidates the genetic basis of rapidly evolving insecticide resistance and will contribute to the development of effective insecticide resistance management strategies. Author summary Insecticide resistance in agricultural pests challenges food security, environmental sustainability, and human health. The cotton bollworm Helicoverpa armigera is resistant to various insecticide classes as well as Bacillus thuringiensis toxins. Understanding the genetic basis of this resistance is crucial for developing effective insecticide resistance management (IRM) strategies. Our study investigated the genetic architecture of resistance of H. armigera to flubendiamide and identified SNPs associated with resistance. We used two approaches: association mapping in wild-derived samples and QTL mapping in a controlled backcross of susceptible and resistant laboratory strains. One specific region on chromosome 2 was found in both GWAS and QTL mapping analysis and showed significant potential as a PCR-based marker for monitoring resistance to flubendiamide in H. armigera . Additionally, the GWAS identified five more SNPs in the field populations. The candidate genes identified are primarily associated with insecticide detoxification mechanisms and calcium homeostasis. Our study advances the understanding of the complex genetic architecture of flubendiamide resistance in H. armigera, providing valuable tools for IRM programs and establishing a basis for future studies.