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• W2079502771 endingPage "1301" @default.
• W2079502771 startingPage "1287" @default.
• W2079502771 abstract "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." @default.
• W2079502771 created "2016-06-24" @default.
• W2079502771 creator A5020027850 @default.
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• W2079502771 creator A5025001398 @default.
• W2079502771 creator A5054564152 @default.
• W2079502771 creator A5080744109 @default.
• W2079502771 creator A5084000403 @default.
• W2079502771 date "2014-05-20" @default.
• W2079502771 modified "2023-10-01" @default.
• W2079502771 title "Genomics of Rapid Adaptation to Antibiotics: Convergent Evolution and Scalable Sequence Amplification" @default.
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