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

Together, the accelerated rate of change and increased entropy at residues 1012 and 1107 suggest that these sites have experienced strong diversifying selection. Our combinatorial genetic studies showed that these particular residues determine receptor tropism, so it is reasonable to conclude that their unique evolution is due to host-range evolution. Mathematical theory has demonstrated that receptor-use evolution should lead to diversification since accessing new host types alters the phages' ecological niches 19 . Indeed, diversification was observed in a related experiment where l evolved to exploit two host cell types with different receptors 20 . To test whether indels at 1012 and 1107 cause diversification, we compared the branches where indels occur versus all others. If the indels cause ecological differentiation, then they should reduce intraspecific competition for hosts and facilitate the long-term maintenance of distinct evolutionary lineages. Indeed, the branches on which indels occur are significantly longer than All rights reserved. No reuse allowed without permission.