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.

One possible alternative explanation for the patterns we observed here, specifically the heightened rates of evolution and elevated levels of diversity, may be that the critical residues in specificity region are prone to mutation. This explanation is unlikely given the evidence from gain-of-function experiments. If the critical residues were prone to mutation, then a diversity of substitutions at those residues should have been observed in the laboratory. Instead, those residues evolved in specific and parallel ways across replicate experiments, indicating the action of strong positive selection. Furthermore, if this variation was due to random mutations and not selection for functional changes, then we would not expect to observe an association between indel evolution and branch length.