Antibiotic resistance is a growing health concern. Efforts to control resistance would benefit from an improved ability to forecast when and how it will evolve. Epistatic interactions between mutations can promote divergent evolutionary trajectories, which complicates our ability to predict evolution. We recently showed that differences between genetic backgrounds can lead to idiosyncratic responses in the evolvability of phenotypic resistance, even among closely related Escherichia coli strains. In this study, we examined whether a strain's genetic background also influences the genotypic evolution of resistance. Do lineages founded by different genotypes take parallel or divergent mutational paths to achieve their evolved resistance states? We addressed this question by sequencing the complete genomes of antibiotic-resistant clones that evolved from several different genetic starting points during our earlier experiments. We first validated our statistical approach by quantifying the specificity of genomic evolution with respect to antibiotic treatment. As expected, mutations in particular genes were strongly associated with each drug. Then, we determined that replicate lines evolved from the same founding genotypes had more parallel mutations at the gene level than lines evolved from different founding genotypes, although these effects were more subtle than those showing antibiotic specificity. Taken together with our previous work, we conclude that historical contingency can alter both genotypic and phenotypic pathways to antibiotic resistance.

抗生素耐药性日益引起人们的健康关注。控制阻力的努力将得益于预测阻力何时以及如何演变的能力。突变之间的上位相互作用可以促进不同的进化轨迹，这使我们预测进化的能力变得复杂。我们最近表明，即使在密切相关的大肠杆菌之间，遗传背景之间的差异也可能导致表型抗性的演变中的特异反应。株。在这项研究中，我们检查了菌株的遗传背景是否也会影响抗性的基因型进化。由不同基因型建立的谱系是否采用平行或发散的突变路径来实现其进化的抗性状态？我们通过对抗生素抗性克隆的完整基因组进行测序来解决这个问题，该克隆是在我们较早的实验中从几个不同的遗传起点进化而来的。我们首先通过量化基因组进化相对于抗生素治疗的特异性来验证我们的统计方法。不出所料，特定基因的突变与每种药物都密切相关。然后，我们确定从相同的创始基因型进化而来的复制品系在基因水平上比从不同的创始基因型进化而来的品系具有更多的平行突变，尽管这些作用比显示抗生素特异性的作用更微妙。结合我们先前的工作，我们得出结论，历史偶然性可以改变抗生素耐药性的基因型和表型途径。