RT Journal Article SR Electronic T1 The roles of history, chance, and natural selection in the evolution of antibiotic resistance JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.07.22.216465 DO 10.1101/2020.07.22.216465 A1 Alfonso Santos-Lopez A1 Christopher W. Marshall A1 Allison L. Welp A1 Caroline Turner A1 Javier Rasero A1 Vaughn S. Cooper YR 2020 UL http://biorxiv.org/content/early/2020/07/22/2020.07.22.216465.abstract AB History, chance, and selection are the fundamental factors that drive and constrain evolution. We designed evolution experiments to disentangle and quantify effects of these forces on the evolution of antibiotic resistance. History was established by prior antibiotic selection of the pathogen Acinetobacter baumannii in both structured and unstructured environments, selection occurred in increasing concentrations of new antibiotics, and chance differences arose as random mutations among replicate populations. The effects of history were reduced by increasingly strong selection in new drugs, but not erased, at times producing important contingencies. Selection in structured environments constrained resistance to new drugs and led to frequent loss of resistance to the initial drug. This research demonstrates that despite strong selective pressures of antibiotics leading to genetic parallelism, history can etch potential vulnerabilities to orthogonal drugs.Competing Interest StatementThe authors have declared no competing interest.