P450 gene duplication and divergence led to the evolution of dual novel functions and insecticide cross-resistance in the brown planthopper Nilaparvata lugens.
P450 gene duplication and divergence led to the evolution of dual novel functions and insecticide cross-resistance in the brown planthopper Nilaparvata lugens.
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DOI：
10.1371/journal.pgen.1010279
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发表时间：
2022-06
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
对许多危害性很大的作物害虫和病媒的可持续控制受到杀虫剂抗药性演变的威胁。因此，已经制定了旨在通过轮换或混合具有不同作用模式（MoA）的杀虫剂来预防或延迟抗性发展的策略。然而，这些方法可能会受到机制的影响，这些机制会对具有不同MoA的杀虫剂产生交叉抗性。尽管交叉抗性的应用重要性，其进化基础仍然知之甚少。在这里，我们揭示了一个单一的基因进化的解毒能力，两个结构无关的杀虫剂与不同的MoA。利用转基因方法，我们证明了细胞色素P450 CYP6ER 1的一个特定的变体，以前被证明赋予抗性的烟碱类吡虫啉在褐飞虱，N。Lugens也赋予对苯基吡唑乙虫腈的交叉抗性。CYP6ER1是重复的耐药菌株，我们表明，虽然收购的突变在两个编码底物识别位点（SRS）的parologs之一导致抗性吡虫啉，不同的一组突变，已知的SRS之外，主要负责对乙虫腈的抗性。这些突变和它们的遗传背景之间的上位性相互作用表明，从相同的基因拷贝的双重抗性的演变涉及功能权衡方面的CYP6ER 1催化活性的乙虫腈与吡虫啉。令人惊讶的是，导致乙虫腈和吡虫啉抗性的突变并不赋予杀虫剂氟虫腈解毒的能力，氟虫腈是另一种与乙虫腈具有密切结构相似性的苯基吡唑。总之，这些发现揭示了基因复制和分化如何导致单个基因进化出多种新功能。从应用的角度来看，他们还展示了如何交叉抗性结构无关的杀虫剂可以演变，并说明在预测代谢机制介导的交叉抗性概况的困难。赋予不同作用模式（MoA）的杀虫剂抗性的机制的演变威胁着破坏用于基于不同MoA的杀虫剂的轮换来管理杀虫剂抗性的主要策略。尽管它很重要，但我们对交叉耐药性如何演变的理解仍然令人惊讶地贫乏。在这里，我们揭示了一个单一的基因，CYP6ER 1，编码细胞色素P450酶，进化抗性的两种杀虫剂的不同的MoA，即烟碱类吡虫啉和苯基吡唑乙虫腈的机制。我们先前已经证明CYP6ER1在褐飞虱的吡虫啉抗性品系中是复制的。lugens。在目前的研究中，我们证明了两组不同的突变，发生在同一拷贝的CYP6ER 1，是关键赋予从头能力，以解毒吡虫啉和乙虫腈。我们揭示了这些突变与其遗传背景之间的复杂相互作用，为与进化的双重抗性相关的功能权衡提供了强有力的证据。我们的研究结果提供了基本的和应用的见解，基因复制的多功能性，在适应性性状的进化过程中提供了功能创新的机会，并揭示了双重新功能可以从单个基因产生的机制。
The sustainable control of many highly damaging insect crop pests and disease vectors is threatened by the evolution of insecticide resistance. As a consequence, strategies have been developed that aim to prevent or delay resistance development by rotating or mixing insecticides with different modes of action (MoA). However, these approaches can be compromised by the emergence of mechanisms that confer cross-resistance to insecticides with different MoA. Despite the applied importance of cross-resistance, its evolutionary underpinnings remain poorly understood. Here we reveal how a single gene evolved the capacity to detoxify two structurally unrelated insecticides with different MoA. Using transgenic approaches we demonstrate that a specific variant of the cytochrome P450 CYP6ER1, previously shown to confer resistance to the neonicotinoid imidacloprid in the brown planthopper, N. lugens, also confers cross-resistance to the phenylpyrazole ethiprole. CYP6ER1 is duplicated in resistant strains, and we show that while the acquisition of mutations in two encoded substrate recognition sites (SRS) of one of the parologs led to resistance to imidacloprid, a different set of mutations, outside of known SRS, are primarily responsible for resistance to ethiprole. Epistatic interactions between these mutations and their genetic background suggest that the evolution of dual resistance from the same gene copy involved functional trade-offs in respect to CYP6ER1 catalytic activity for ethiprole versus imidacloprid. Surprisingly, the mutations leading to ethiprole and imidacloprid resistance do not confer the ability to detoxify the insecticide fipronil, another phenylpyrazole with close structural similarity to ethiprole. Taken together, these findings reveal how gene duplication and divergence can lead to the evolution of multiple novel functions from a single gene. From an applied perspective they also demonstrate how cross-resistance to structurally unrelated insecticides can evolve, and illustrate the difficulty in predicting cross-resistance profiles mediated by metabolic mechanisms. The evolution of mechanisms that confer resistance to insecticides of different mode of action (MoA) threatens to undermine the primary strategy used to manage insecticide resistance based on the rotation of insecticides of different MoA. Despite its importance, our understanding of how cross-resistance evolves remains surprisingly poor. Here, we uncover the mechanisms by which a single gene, CYP6ER1, encoding a cytochrome P450 enzyme, evolved resistance to two insecticides of different MoA, namely the neonicotinoid imidacloprid and the phenylpyrazole ethiprole. We have previously shown that CYP6ER1 is duplicated in imidacloprid resistant strains of the brown planthopper, N. lugens. In the current study we demonstrate that two different sets of mutations, occurring in the same copy of CYP6ER1, were key to conferring the de novo ability to detoxify imidacloprid and ethiprole. We uncover complex interactions between these mutations and their genetic background that provide strong evidence of functional trade-offs associated with evolving dual resistance. Our findings provide fundamental and applied insights into the versatility of gene duplication in providing opportunities for functional innovation during the evolution of adaptive traits and reveal the mechanisms by which dual novel functions can arise from single genes.
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影响因子：
8
作者：
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影响因子：
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