Incipient resistance to an effective pesticide results from genetic adaptation and the canalization of gene expression

The resistance of bacteria, disease vectors, and pests to chemical controls has vast ecological, economic, and human-health costs. In most cases, resistance is only detected after non-susceptible phenotypes have spread throughout the entire population. Detecting resistance in its incipient stages, by comparison, provides time to implement preventative strategies. Incipient resistance (IR) can be detected by coupling standard toxicology assays with large-scale gene expression experiments. We apply this approach to a system where an invasive parasite, sea lamprey (Petromyzon marinus), has been treated with the highly-effective pesticide 3-trifluoromethyl-4-nitrophenol (TFM) for 60 years. Toxicological experiments revealed that lamprey from treated populations did not have higher survival to TFM exposure than lamprey from their native range, demonstrating that full-fledged resistance has not yet evolved. In stark contrast, we find hundreds of genes differentially expressed in response to TFM in the population with the longest history of exposure, many of which relate to TFM9s primary mode of action, the uncoupling of oxidative phosphorylation. One gene critical to oxidative phosphorylation, ATP5PB, which encodes subunit b of ATP synthase, was nearly fixed for alternative alleles in comparisons between native and treated populations (FST > 9 SD from the mean). A gene encoding an additional subunit of ATP synthase, ATP5F1B, was canalized for high expression in treated populations, but remained plastic in response to treatment in sea lamprey from the native range. These combined genomic and transcriptomic results illustrate that an adaptive, genetic response to TFM is driving incipient resistance in a damaging pest species.