Delayed commitment to evolutionary fate in antibiotic resistance fitness landscapes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Adam C. Palmer, Erdal Toprak, Michael Baym, Seungsoo Kim, Adrian Veres, Shimon Bershtein, Roy Kishony

ABSTRACT

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 peak; while they restrict the number of direct paths, they generate more indirect paths, where mutations are adaptively gained and later adaptively lost or changed. This enhanced accessibility allows evolution to proceed through many adaptive steps while delaying commitment to genotypic fate, hindering our ability to predict or control evolutionary outcomes. More... »

PAGES

7385

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms8385

DOI

http://dx.doi.org/10.1038/ncomms8385

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053491779

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26060115


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