Biosciences, University of Exeter, Penryn TR10 9EZ, United Kingdom.
Genetics. 2013 Aug;194(4):807-15. doi: 10.1534/genetics.112.141895.
The past 60 years have seen a revolution in our understanding of the molecular genetics of insecticide resistance. While at first the field was split by arguments about the relative importance of mono- vs. polygenic resistance and field- vs. laboratory-based selection, the application of molecular cloning to insecticide targets and to the metabolic enzymes that degrade insecticides before they reach those targets has brought out an exponential growth in our understanding of the mutations involved. Molecular analysis has confirmed the relative importance of single major genes in target-site resistance and has also revealed some interesting surprises about the multi-gene families, such as cytochrome P450s, involved in metabolic resistance. Identification of the mutations involved in resistance has also led to parallel advances in our understanding of the enzymes and receptors involved, often with implications for the role of these receptors in humans. This Review seeks to provide an historical perspective on the impact of molecular biology on our understanding of resistance and to begin to look forward to the likely impact of rapid advances in both sequencing and genome-wide association analysis.
过去的 60 年见证了我们对杀虫剂抗性的分子遗传学理解的一场革命。虽然起初该领域因关于单基因与多基因抗性以及田间与实验室选择的相对重要性的争论而分裂,但将分子克隆应用于杀虫剂靶标以及在杀虫剂到达靶标之前降解它们的代谢酶,使得我们对所涉及的突变有了指数级的理解。分子分析证实了单个主要基因在靶标抗性中的相对重要性,也揭示了一些关于多基因家族(如细胞色素 P450s)的有趣惊喜,这些基因家族参与代谢抗性。抗性涉及的突变的鉴定也导致了我们对涉及的酶和受体的理解的平行进展,这通常对这些受体在人类中的作用具有重要意义。这篇综述试图从历史角度探讨分子生物学对我们对抗性的理解的影响,并开始展望测序和全基因组关联分析的快速进展可能带来的影响。