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.

As repositories of gene and protein sequences grow and biologists begin to gain access to the overwhelming genetic diversity of life, researchers are faced with the challenge of uncovering the relatively few mutations that are functionally important and evolutionarily significant. By combining laboratory evolution experiments with genome editing, we were able to identify protein residues with important functional consequences that have remarkable evolutionary properties, including disproportionate levels of heterogeneity and elevated rates of evolution. Given the concordance between evolutionary rates at critical residues in laboratory and natural populations, we posit that these properties of the natural variation are due to positive selection for receptor usage and host-range expansion.