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Delayed commitment to evolutionary fate in antibiotic resistance fitness landscapes.

Nat Commun.. 2015-06; 
Palmer AC#,, Toprak E#, Baym M, Kim S, Veres A, Bershtein S, Kishony R.
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摘要

Predicting evolutionary paths to antibiotic resistance is key for understanding and controlling drug resistance. When considering a single final resistant genotype, epistatic contingencies among mutations restrict evolution to a small number of adaptive paths. Less attention has been given to multi-peak landscapes, and while specific peaks can be favoured, it is unknown whether and how early a commitment to final fate is made. Here we characterize a multi-peaked adaptive landscape for trimethoprim resistance by constructing all combinatorial alleles of seven resistance-conferring mutations in dihydrofolate reductase. We observe that epistatic interactions increase rather than decrease the accessibility of each ... More

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