TY - JOUR T1 - Balance between promiscuity and specificity in phage λ host range JF - bioRxiv DO - 10.1101/2020.06.25.171868 SP - 2020.06.25.171868 AU - Bryan Andrews AU - Stanley Fields Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/06/26/2020.06.25.171868.abstract N2 - As hosts acquire resistance to viruses, viruses must overcome that resistance to re-establish infectivity, or go extinct. Despite the significant hurdles associated with adapting to a resistant host, viruses are evolutionarily successful and maintain stable coevolutionary relationships with their hosts. To investigate the factors underlying how pathogens adapt to their hosts, we performed a deep mutational scan of the region of the λ tail fiber tip protein that mediates contact with the λ host, E. coli. Phages harboring amino acid substitutions were subjected to selection for infectivity on wild type E. coli, revealing a highly restrictive fitness landscape, in which most substitutions completely abrogate function. By comparing this lack of mutational tolerance to evolutionary diversity, we highlight a set of mutationally intolerant and diverse positions associated with host range expansion. Imposing selection for infectivity on three λ-resistant hosts, each harboring a different missense mutation in the λ receptor, reveals hundreds of adaptive variants in λ. We distinguish λ variants that confer promiscuity, a general ability to overcome host resistance, from those that drive host-specific infectivity. Both processes may be important in driving adaptation to a novel host.Competing Interest StatementThe authors have declared no competing interest. ER -