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.

Based on the patterns of J variation we observe, 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 predict host shifts in natural populations. Such an approach is in the same spirit as pioneering work by Barlow and Hall, who had success in predicting the evolution of antibiotic resistance by combining evolution experiments with analyses of natural and clinical isolates (Hall 2002; Barlow and Hall 2003; Hall 2004; Salverda et al. 2010) . In particular, worrisome mutations can be identified with experiments as described here or with other laboratory techniques such as deep mutational scanning (Bloom 2017) . This information can be combined with genomic surveillance efforts (Gire et al. 2014; Grubaugh et al. 2017) to devise better strategies to eradicate potential pandemics.