Genomics of rapid adaptation to antibiotics: convergent evolution and scalable sequence amplification.
Evolutionary adaptation can be extremely fast, especially in response to high selection intensities. A prime example is the surge of antibiotic resistance in bacteria. The genomic underpinnings of such rapid changes may provide information on the genetic processes that enhance fast responses and the particular trait functions under selection. Here, we use experimentally evolved Escherichia coli for a detailed dissection of the genomics of rapid antibiotic resistance evolution. Our new analyses demonstrate that amplification of a sequence region containing several known antibiotic resistance genes represents a fast genomic response mechanism under high antibiotic stress, here exerted by drug combination. In particular, higher dosage of such antibiotic combinations coincided with higher copy number of the sequence region. The amplification appears to be evolutionarily costly, because amplification levels rapidly dropped after removal of the drugs. Our results suggest that amplification is a scalable process, as copy number rapidly changes in response to the selective pressure encountered. Moreover, repeated patterns of convergent evolution were found across the experimentally evolved bacterial populations, including those with lower antibiotic selection intensities. Intriguingly, convergent evolution was identified on different organizational levels, ranging from the above sequence amplification, high variant frequencies in specific genes, prevalence of individual nonsynonymous mutations to the unusual repeated occurrence of a particular synonymous mutation in Glycine codons. We conclude that constrained evolutionary trajectories underlie rapid adaptation to antibiotics. Of the identified genomic changes, sequence amplification seems to represent the most potent, albeit costly genomic response mechanism to high antibiotic stress.
Department of Evolutionary Ecology and Genetics, University of Kiel, Germany.
David
D
Laehnemann
Biosciences, Geoffrey Pope Building, University of Exeter, United KingdomDepartment of Zoology, University of Oxford, United Kingdom.
Rafael
R
Peña-Miller
Institute for Clinical Molecular Biology, University of Kiel, Germany.
Philip
P
Rosenstiel
Biosciences, Geoffrey Pope Building, University of Exeter, United Kingdom.
Robert
R
Beardmore
Department of Evolutionary Ecology and Genetics, University of Kiel, Germany gjansen@zoologie.uni-kiel.de hschulenburg@zoologie.uni-kiel.de.
Gunther
G
Jansen
Department of Evolutionary Ecology and Genetics, University of Kiel, Germany gjansen@zoologie.uni-kiel.de hschulenburg@zoologie.uni-kiel.de.
Hinrich
H
Schulenburg
D000222:Adaptation, Physiological; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003062:Codon; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000235:genetics; D019143:Evolution, Molecular; D016680:Genome, Bacterial / Q000187:drug effects*; D006801:Humans; D009154:Mutation
D000900:Anti-Bacterial Agents; D003062:Codon; D029968:Escherichia coli Proteins
Escherichia coli; MC4100; antibiotic resistance; experimental evolution; population genomics; synonymous codon