Viral gain-of-function experiments uncover residues under diversifying selection in nature

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

The congruence we find between laboratory and natural evolution in l contrasts with work showing that beneficial mutations in Richard Lenski's long-term experiment anti- Together, these studies show that selection experiments on viruses cultured in the laboratory can inform evolution in nature. Based on the patterns of J sequence variation observed, we suggest that host-range evolution is common in this group of viruses, and perhaps others too. While the frequency of host-range evolution may be unsettling, our work also demonstrates potential methods to combat host shifts. In particular, worrisome mutations can be identified with functional genetic experiments as described here or with other laboratory techniques such as deep mutational scanning 23 . This information can be combined with genomic surveillance efforts underway 24,25 to devise more effective disease management strategies to eradicate problematic strains.