Gain-of-function experiments with bacteriophage lambda uncover residues under diversifying selection in nature

Maddamsetti, Rohan; Johnson, Daniel T.; Spielman, Stephanie J.; Petrie, Katherine L.; Marks, Debora S.; Meyer, Justin R.

Ideally, evolution experiments could accelerate our understanding of host-range shifts; however, it is not clear whether host-range shifts observed in the laboratory can faithfully inform us about host-range shifts in nature, for at least two reasons. First, evolutionary trajectories might be sensitive to differences in environmental conditions between the laboratory and nature. Second, the number of evolutionary paths sampled in laboratory experiments is very small compared to natural virus diversity due to the enormous size of viral populations. Indeed, some researchers have called for the suspension of gain-of-function experiments on the grounds that they would tell us little about real-world evolution at the risk of constructing pandemic strains (Casadevall and Imperiale 2014) .