PT - JOURNAL ARTICLE AU - Maddamsetti, Rohan AU - Johnson, Daniel T. AU - Spielman, Stephanie J. AU - Petrie, Katherine L. AU - Marks, Debora S. AU - Meyer, Justin R. TI - Viral gain-of-function experiments uncover residues under diversifying selection in nature AID - 10.1101/242495 DP - 2018 Jan 01 TA - bioRxiv PG - 242495 4099 - http://biorxiv.org/content/early/2018/01/03/242495.short 4100 - http://biorxiv.org/content/early/2018/01/03/242495.full AB - Viral gain-of-function mutations are commonly observed in the laboratory; however, it is unknown whether those mutations also evolve in nature. We identify two key residues in the host recognition protein of bacteriophage λ that are necessary to exploit a new receptor; both residues repeatedly evolved among homologs from environmental samples. Our results provide evidence for widespread host-shift evolution in nature and a proof of concept for integrating experiments with genomic epidemiology.