Biointeractions and Crop Protection Department, Rothamsted Research, Harpenden, Hertfordshire, UK.
NIAB, Cambridge, UK.
Mol Ecol. 2021 Nov;30(21):5318-5327. doi: 10.1111/mec.15877. Epub 2021 Mar 22.
The evolution of resistance has been seen across all major classes of xenobiotics, including antimicrobial drugs and agricultural pesticides. This repeated emergence of resistance is a case of phenotypic parallel evolution, but often the parallelism extends to the molecular level too, with multiple species gaining the same mutation in response to the same chemical treatment. We review the degree of repeatability in target-site resistance mutations affecting different classes of site-specific agricultural fungicides used in crop protection, comparing the extent to which resistance in different pathogen species has evolved via the same or different mutations. For all major fungicide target sites, substantial levels of molecular parallel evolution can be seen, with at least one mutation recurring in over 50% of species. Target-site mutations appear to be most repeatable in cytochrome b, target site of quinone-outside inhibitor fungicides, and least predictable for CYP51, target site of the azoles. Intermediate levels of repeatability are seen for the MBC target site β-tubulin, and the SDHI target site succinate dehydrogenase. Repeatability may be lower where there are selective trade-offs between resistance and pleiotropic fitness penalties, or differing levels of cross-resistance across members of a fungicide class; or where single mutations confer only partial resistance, and epistatic interactions between multiple mutations result in a rugged fitness landscape. This affects the predictive power of in vitro mutation studies, and has practical implications for resistance monitoring strategies and diagnostic methods.
抗药性的进化在所有主要的外源化学物类别中都有出现，包括抗菌药物和农业用杀虫剂。这种抗药性的反复出现是表型平行进化的一个例子，但这种平行性往往也延伸到分子水平，多种物种因对同一化学处理而获得相同的突变。我们回顾了影响作物保护中使用的不同类别的、针对特定靶标的农业杀菌剂的靶标抗性突变的可重复性程度，比较了不同病原体物种因相同或不同突变而进化出抗药性的程度。对于所有主要的杀菌剂靶标，都可以看到大量的分子平行进化，至少有一个突变在超过 50%的物种中反复出现。靶标突变在细胞色素 b 中最为可重复，细胞色素 b 是醌类抑制剂杀菌剂的靶标，而在 CYP51 中则最不可预测，CYP51 是唑类药物的靶标。MBC 靶标β-微管蛋白和 SDHI 靶标琥珀酸脱氢酶的可重复性处于中等水平。如果在抗药性和多效性适应值之间存在选择性权衡、在杀菌剂类别中的成员之间存在不同程度的交叉抗药性、或者单个突变只赋予部分抗药性，并且多个突变之间存在上位性相互作用，那么可重复性可能会降低。这会影响体外突变研究的预测能力，对抗药性监测策略和诊断方法有实际影响。
