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Updated: Jul 17, 2026

Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
Experimental evolution of gene duplicates in a bacterial plasmid model
Alisha K Holloway1, Timothy Palzkill, James J Bull
1Section of Evolution and Ecology, Center for Population Biology, University of California, Davis, CA 95616, USA. akholloway@ucdavis.edu
Gene duplication and diversifying selection were tested in bacteria. While one gene copy evolved resistance to a new drug, maintaining both copies proved costly, leading to plasmid loss and hindering functional divergence.
Area of Science:
- Evolutionary biology
- Microbial genetics
Background:
- Gene duplication is a key driver of evolutionary innovation.
- Diversifying selection can favor the divergence of duplicated genes for new functions.
- The TEM-1 beta-lactamase gene provides a model for studying drug resistance evolution.
Purpose of the Study:
- To experimentally test the fate of gene duplicates under diversifying selection for dual drug resistance.
- To investigate the evolutionary trade-offs associated with maintaining gene copies under antibiotic pressure.
Main Methods:
- Bacterial system (E. coli) with two identical TEM-1 beta-lactamase genes on compatible plasmids.
- Experimental evolution under selection for both ampicillin and cefotaxime resistance.
- Quantitative assessment of plasmid maintenance and bacterial growth fitness.
Main Results:
- One beta-lactamase gene copy evolved increased cefotaxime resistance.
- The cefotaxime-resistant plasmid retained partial ampicillin resistance.
- Maintenance of both gene copies under increasing antibiotic concentrations led to plasmid loss or inhibited cell growth, contradicting models.
- Significant fitness costs were associated with carrying duplicate genes under dual drug selection.
Conclusions:
- The study highlights the critical role of gene dosage costs in limiting the evolution of functional divergence in gene duplicates.
- A quantitative trade-off exists between the benefits of duplicated genes and their associated fitness costs.
- Experimental evolution revealed constraints on the maintenance of gene duplicates under strong diversifying selection.
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