There is a pressing need to identify the molecular mechanisms underlying the, often magnifying, interactive effects between contaminants and natural stressors. Here we test our hypothesis that lower general stress defence responses contribute to synergistic interactions between stressors. We focus on the widespread pattern that many contaminants are more toxic at higher temperatures. Specifically, we tested the effects of an environmentally realistic low‐effect and high‐effect concentration of the pesticide chlorpyrifos under warming at the gene expression level in the northern house mosquito Culex pipiens molestus (Forskal, 1775). By applying the independent action model for combined stressors on RNA‐sequencing data, we identified interactive gene expression patterns under combined exposure to chlorpyrifos and warming for general stress defence responses: protection of macromolecules, antioxidant processes, detoxification and energy metabolism/allocation. Most of these general stress defence response genes showed upregulated antagonistic interactions (i.e., were less upregulated than expected under the independent action model). This indicates that when pesticide exposure was combined with warming, the general stress defence responses were no longer buffering increased stress levels, which may contribute to a higher sensitivity to toxicants under warming. These upregulated antagonistic interactions were stronger for the high‐effect chlorpyrifos concentration, indicating that exposure to this concentration under warming was most stressful. Our results highlight that quantitative analysis of the frequency and strength of the interaction types of general stress defence response genes, specifically focusing on antagonistic upregulations and synergistic downregulations, may advance our understanding of how natural stressors modify the toxicity of contaminants.

中文翻译：

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降低的胁迫防御反应导致农药在变暖下具有更高的毒性

迫切需要确定污染物和自然应激源之间相互作用效应（通常是放大效应）的分子机制。在这里，我们检验了以下假设：较低的一般压力防御反应有助于压力源之间的协同相互作用。我们关注的是一种普遍的模式，即许多污染物在高温下更具毒性。具体来说，我们在北方房屋蚊虫库蚊（Culex pipiens molestus）的基因表达水平下，研究了在升温条件下环境友好的低效和高效农药毒死rif的影响。（福尔斯卡尔，1775年）。通过在RNA测序数据上应用针对联合应激源的独立作用模型，我们确定了在毒死combined暴露和升温条件下针对一般胁迫防御反应的相互作用基因表达模式：保护大分子，抗氧化过程，排毒和能量代谢/分配。这些一般的应激防御反应基因中的大多数显示出拮抗相互作用的上调（即，与独立作用模型下的预期相比，上调程度较小）。这表明，当农药暴露与温度升高相结合时，一般的胁迫防御反应不再能缓解压力水平的升高，这可能有助于在温度升高下对毒物的敏感性更高。在高效毒死rif浓度下，这些上调的拮抗作用更强，表明在升温下暴露于该浓度的压力最大。我们的研究结果表明，对一般胁迫防御反应基因相互作用类型的频率和强度进行定量分析，尤其是集中在拮抗性上调和协同下调上，可以增进我们对自然应激源如何改变污染物毒性的理解。