Path-dependent evolutionary trajectories diversifies the adaptation rates to antibiotics in Escherichia coli

Although the evolution of organisms is predicted to be driven and constrained by chance, natural selection and evolutionary trajectories, specifically, how the evolutionary trajectories affect evolutionary outcomes poorly understood. Here, we report a two-step experimental evolution study showing that different kanamycin exposure regimes lead to divergent evolutionary trajectories that significantly affect the adaptation rates of Escherichia coli to antibiotics. Populations under mild, periodic or irregular selection regimes evolved similar level of resistance, while populations under strong selection displayed the highest level of resistance with the presence of kanamycin. Whole-genome sequencing resulted that only the populations under strong selection acquired SNP mutations in the gene crl. Notably, in the absence of antibiotics, populations with different selection histories exhibited significant differences in antibiotic resistance and adaptive rates. These differences were driven by divergent resistance evolutionary trajectories, even though the populations reached similar levels of resistance under different selection regimes. These results highlight that the evolutionary outcomes of bacterial antibiotic resistance were influenced by environmental change regimes, and different evolutionary trajectory diversified the adaptation rates in new environments. Together, our findings demonstrate that evolutionary trajectories—determined by historical selection regimes—play a crucial role in shaping evolutionary outcomes, offering new insights into the predictability and contingency of evolutionary processes.