Artificial Gene Amplification in Escherichia coli Reveals Numerous Determinants for Resistance to Metal Toxicity. Author Kenric Hoegler, Michael Hecht Publication Year 2018 Type Journal Article Abstract When organisms are subjected to environmental challenges, including growth inhibitors and toxins, evolution often selects for the duplication of endogenous genes, whose overexpression can provide a selective advantage. Such events occur both in natural environments and in clinical settings. Microbial cells-with their large populations and short generation times-frequently evolve resistance to a range of antimicrobials. While microbial resistance to antibiotic drugs is well documented, less attention has been given to the genetic elements responsible for resistance to metal toxicity. To assess which overexpressed genes can endow gram-negative bacteria with resistance to metal toxicity, we transformed a collection of plasmids overexpressing all E. coli open reading frames (ORFs) into naive cells, and selected for survival in toxic concentrations of six transition metals: Cd, Co, Cu, Ni, Ag, Zn. These selections identified 48 hits. In each of these hits, the overexpression of an endogenous E. coli gene provided a selective advantage in the presence of at least one of the toxic metals. Surprisingly, the majority of these cases (28/48) were not previously known to function in metal resistance or homeostasis. These findings highlight the diverse mechanisms that biological systems can deploy to adapt to environments containing toxic concentrations of metals. Keywords Gene Expression Regulation, Bacterial, Escherichia coli, Anti-Bacterial Agents, Escherichia coli Proteins, Open Reading Frames, Evolution, Molecular, Plasmids, Gene Amplification, Metals, Nucleic Acid Amplification Techniques Journal J Mol Evol Volume 86 Issue 2 Pages 103-110 Date Published 2018 Feb ISSN Number 1432-1432 DOI 10.1007/s00239-018-9830-3 Alternate Journal J Mol Evol PMCID PMC6116729 PMID 29356848 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML