Integrated genomic and transcriptomic approaches reveal oxidative stress adaptation mechanisms in a mesotrione‐resistant Amaranthus tuberculatus biotype

BACKGROUND: Amaranthus tuberculatus (waterhemp) is a major agricultural weed known for its rapid evolution of resistance to multiple herbicide modes-of-action. Resistance to 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors such as mesotrione is particularly concerning, yet the underlying genetic and molecular mechanisms remain incompletely understood. This study investigated the basis of mesotrione resistance in a Canadian waterhemp population (biotype 714) using an integrated genomic and transcriptomic approach. RESULTS: ). Gene Ontology (GO) enrichment of genes proximal to these SNPs implicated pathways related to electron transport and oxidoreductase activity. Transcriptomic analysis of treated plants revealed 187 differentially expressed genes (DEGs) between resistant and susceptible phenotypes. GO enrichment of these genes highlighted significant upregulation of pathways related to redox homeostasis, glutathione metabolism, lipid signaling and secondary metabolism. Weighted Gene Co-expression Network Analysis (WGCNA) further corroborated these findings, identifying gene modules correlated with resistance that were enriched for functions in oxidative stress response and detoxification. CONCLUSION: Mesotrione resistance in this A. tuberculatus population is a complex, polygenic trait. Our findings indicate that resistance is not conferred by a single mechanism, but rather by an enhanced metabolic capacity to mitigate herbicide-induced oxidative stress. This multifaceted defense involves the coordinated regulation of numerous detoxification, signaling, and metabolic pathways. Understanding this complex form of nontarget-site resistance (NTSR) is critical for devising future management strategies to combat the spread of herbicide-resistant weeds. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.