Mistranslation can promote the exploration of alternative evolutionary trajectories in enzyme evolution.

ABSTRACT: Darwinian evolution preferentially follows mutational pathways whose individual steps increase fitness. Alternative pathways with mutational steps that do not increase fitness are less accessible. Here, we show that mistranslation, the erroneous incorporation of amino acids into nascent proteins, can increase the accessibility of such alternative pathways and, ultimately, of high fitness genotypes. We subject populations of the beta-lactamase TEM-1 to directed evolution in Escherichia coli under both low- and high-mistranslation rates, selecting for high activity on the antibiotic cefotaxime. Under low mistranslation rates, different evolving TEM-1 populations ascend the same high cefotaxime-resistance peak, which requires three canonical DNA mutations. In contrast, under high mistranslati

SUBMITTER: Zheng J 

PROVIDER: S-EPMC8457080 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature