The resistance of pest species to chemical controls has vast ecological, economic, and societal costs. In most cases, resistance is only detected after spreading throughout an entire population. Detecting resistance in its incipient stages, by comparison, provides time to implement preventative strategies. Incipient resistance 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 untreated populations, demonstrating that full‐fledged resistance has not yet evolved. In 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 TFM’s primary mode of action, the uncoupling of oxidative phosphorylation, and subsequent depletion of ATP. Three genes critical to oxidative phosphorylation, ATP5PB, PLCB1, and NDUFA9, were nearly fixed for alternative alleles in comparisons of SNPs between treated and untreated populations (F_ST > 5 SD from the mean). ATP5PB encodes subunit b of ATP synthase and an additional subunit, ATP5F1B, was canalized for high expression in treated populations, but remained plastic in response to TFM treatment in individuals from the untreated population. These combined genomic and transcriptomic results demonstrate that an adaptive, genetic response to TFM is likely driving incipient resistance in a damaging pest species.

中文翻译：

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对有效农药的初期抗药性来自基因适应和基因表达的渠道化

害虫对化学控制的抵抗力具有巨大的生态，经济和社会成本。在大多数情况下，只有在散布到整个人群后才能检测到抗药性。相比之下，在起步阶段检测抗药性为实施预防策略提供了时间。可以通过将标准毒理学分析与大规模基因表达实验相结合来检测初期抗药性。我们将此方法应用于侵入性寄生虫，海七lamp（Petromyzon marinus））已用高效农药3-三氟甲基-4-硝基苯酚（TFM）处理了60年。毒理学实验表明，经处理种群的七lamp鳗对TFM暴露的存活率不高于未经处理种群的七rey鳗，表明尚未形成完全的抗药性。相反，我们发现在暴露时间最长的人群中，数百种基因对TFM的反应差异表达，其中许多与TFM的主要作用方式，氧化磷酸化的解偶联以及随后的ATP消耗有关。在治疗和未治疗人群之间比较SNP时，对于其他等位基因来说，对于氧化磷酸化至关重要的三个基因ATP5PB，PLCB1和NDUFA9几乎固定了（F _ST  > 5 SD。ATP5PB编码ATP合酶b的亚基，另外一个亚基ATP5F1B可以在受治疗的人群中高表达，但在未受治疗的人群中响应TFM治疗仍保持可塑性。这些综合的基因组和转录组结果证明，对TFM的适应性遗传反应很可能会在有害的有害生物物种中引发初期抗性。