ArticleProceedings of the National Academy of Sciences of the United States of America2011
Artificial gene amplification reveals an abundance of promiscuous resistance determinants in Escherichia coli.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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62 citing papers in PubMed, 119 citations in OpenAlex.
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- Mutations Elevate an Underground Pathway to a Physiologically Relevant Protopathway.Molecular biology and evolution · 2025Article
- A Cryptic Prophage Transcription Factor Drives Phenotypic Changes via Host Gene Regulation.bioRxiv : the preprint server for biology · 2024Article
- Intraspecific variation in antibiotic resistance potential withinMicrobiology spectrum · 2024Article
- The Pseudomonas aeruginosa Resistome: Permanent and Transient Antibiotic Resistance, an Overview.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Molecular Typing ofJournal of pharmacy & bioallied sciences · 2023Article
- Multicopy suppressor screens reveal convergent evolution of single-gene lysis proteins.Nature chemical biology · 2023Article
- Growth-mediated negative feedback shapes quantitative antibiotic response.Molecular systems biology · 2022Article
- Low-cost anti-mycobacterial drug discovery using engineered E. coli.Nature communications · 2022Article
- Transcription Factor SrsR (YgfI) Is a Novel Regulator for the Stress-Response Genes in Stationary Phase inInternational journal of molecular sciences · 2022Article
- Gene Amplification Uncovers Large Previously Unrecognized Cryptic Antibiotic Resistance Potential in E. coli.Microbiology spectrum · 2021Article
- Article
- Genome-Wide Screening of Oxidizing Agent Resistance Genes inAntioxidants (Basel, Switzerland) · 2021Article
- Use of Transposon Directed Insertion-Site Sequencing to Probe the Antibacterial Mechanism of a Model Honey onFrontiers in microbiology · 2021Article
- Assessing the genomic relatedness and evolutionary rates of persistent verotoxigenicMicrobial genomics · 2020Article
- How enzyme promiscuity and horizontal gene transfer contribute to metabolic innovation.The FEBS journal · 2020Review
- Novel Target Exploration from Hypothetical Proteins ofFrontiers in cellular and infection microbiology · 2020Article
2 more citing papers are in PubMed but not listed here.
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3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Duplicated genes provide an important raw material for adaptive evolution. However, the relationship between gene duplication and the emergence of new biochemical functions is complicated, and it has been difficult to quantify the likelihood of evolving novelty in any systematic manner. Here, we describe a comprehensive search for artificially amplified genes that are able to impart new phenotypes on Escherichia coli, provided their expression is up-regulated. We used a high-throughput, library-on-library strategy to screen for resistance to antibiotics and toxins. Cells containing a complete E. coli ORF library were exposed to 237 toxin-containing environments. From 86 of these environments, we identified a total of 115 cases where overexpressed ORFs imparted improved growth. Of the overexpressed ORFs that we tested, most conferred small but reproducible increases in minimum inhibitory concentration (≤16-fold) for their corresponding antibiotics. In many cases, proteins were acting promiscuously to impart resistance. In the absence of toxins, most strains bore no fitness cost associated with ORF overexpression. Our results show that even the genome of a nonpathogenic bacterium harbors a substantial reservoir of resistance genes, which can be readily accessed through overexpression mutations. During the growth of a population under selection, these mutations are most likely to be gene amplifications. Therefore, our work provides validation and biochemical insight into the innovation, amplification, and divergence model of gene evolution under continuous selection [Bergthorsson U, Andersson DI, Roth JR (2007) Proc Natl Acad Sci USA 104:17004-17009], and also illustrates the high frequency at which novel traits can evolve in bacterial populations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.