进化得与失之间的权衡在自然界中很普遍，但其遗传基础尚未得到很好的解决。昆虫对杀虫剂的抗性的进化通常与强大的适应性成本相关。然而，对于健身权衡如何运作仍然知之甚少。在这里，我们表明丝裂原激活蛋白激酶（MAPK）途径及其上游和下游参与者是粉虱烟粉虱与杀虫剂抗性相关的适应性权衡的基础。具体来说，我们发现了一个关键的细胞色素 P450 基因 CYP6CM1，该基因赋予烟粉虱对新烟碱类杀虫剂的抗性，该基因由 MAPK p38 和 ERK 通过激活转录因子 cAMP 响应元件结合蛋白来调节。然而，p38 和 ERK 的磷酸化也会导致转录抑制因子 Cap“n” 项圈同种型 C (CncC) 的激活，从而负向调控 exuperantia (Ex)、vasa (Va) 和良性角细胞肿瘤 (Bg) 等关键基因参与卵子发生，导致卵巢生长异常和女性生育力下降。我们进一步证明跨膜 G 蛋白偶联受体 (GPCR) 神经肽 FF 受体 2 (NPFF2) 通过磷酸化触发 p38 和 ERK 通路。此外，p38 和 NPFF2 之间的正反馈循环导致 MAPK 途径持续激活，从而持续促进新烟碱类耐药性，但会带来显着的繁殖成本。总的来说，这些发现为 GPCR-MAPK 信号通路在进化权衡中产生的顺反调节网络的作用提供了基本见解，并为可持续害虫防治策略的制定提供了应用知识。

Trade-offs between evolutionary gain and loss are prevalent in nature, yet their genetic basis is not well resolved. The evolution of insect resistance to insecticide is often associated with strong fitness costs; however, how the fitness trade-offs operates remains poorly understood. Here, we show that the mitogen-activated protein kinase (MAPK) pathway and its upstream and downstream actors underlie the fitness trade-offs associated with insecticide resistance in the whitefly Bemisia tabaci. Specifically, we find a key cytochrome P450 gene CYP6CM1, that confers neonicotinoids resistance to in B. tabaci, is regulated by the MAPKs p38 and ERK through their activation of the transcription factor cAMP-response element binding protein. However, phosphorylation of p38 and ERK also leads to the activation of the transcription repressor Cap "n" collar isoform C (CncC) that negatively regulates exuperantia (Ex), vasa (Va), and benign gonial cell neoplasm (Bg), key genes involved in oogenesis, leading to abnormal ovary growth and a reduction in female fecundity. We further demonstrate that the transmembrane G protein-coupled receptor (GPCR) neuropeptide FF receptor 2 (NPFF2) triggers the p38 and ERK pathways via phosphorylation. Additionally, a positive feedback loop between p38 and NPFF2 leads to the continuous activation of the MAPK pathways, thereby constitutively promoting neonicotinoids resistance but with a significant reproductive cost. Collectively, these findings provide fundamental insights into the role of cis-trans regulatory networks incurred by GPCR-MAPK signaling pathways in evolutionary trade-offs and applied knowledge that can inform the development of strategies for the sustainable pest control.