A dose-response transcriptome of the honey bee by characterizing gene expression across a large range of oxidative stress

Stress response in insects is often studied through single behaviors, traits, or genes to identify quantitative impacts of sublethal or lethal stress dosages. While this approach has been used to study stressors and beneficial treatments in honey bees, regulatory testing of stressors rarely combines a range of doses with numerous biological outcomes to distinguish molecular signatures of survivable and lethal dosages. Using a cost-efficient Tagseq approach, we study the dose-response of the honey bee transcriptome to the oxidative stressor paraquat, an herbicide that induces oxidative stress in a wide variety of organisms. Across nine doses, we vary the stress 30-fold and evaluate the physiological responses in 91 whole transcriptome profiles along with concurrent measures of survival per dose. We are able to distinguish how the bees’ transcriptome reacts to sublethal versus lethal doses and identify key biological processes underlying oxidative stress resistance. Most notably, we find a strong and consistent downregulation of several key genes in the sex determination pathway in response to paraquat exposure, including the master regulator Complementary Sex Determiner ( csd ). This study identifies previously unknown associations between the sex determination pathway and oxidative stress, and our novel approach of combining extensive dosage transcriptomes with a survival study provides greater detail to understand this association and better define molecular signatures of sublethal and lethal dosages of oxidative stress.