Cross-scale dynamics and the evolutionary emergence of infectious diseases

Sebastian J. Schreiber; Ruian Ke; Claude Loverdo; Miran Park; Priyanna Ahsan; James O. Lloyd-Smith

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/066688 doi: bioRxiv preprint which pass through a fitness valley, then the scale at which this valley occurs matters. A within-host fitness valley in replication rates would hinder pathogens with long-term infections and larger bottleneck widths, more than those with smaller bottlenecks. A between-host fitness valley in transmissibility could hinder evolutionary emergence of pathogens causing long-term infections more than those causing short-term infections, unless the within-host landscape is sufficiently favorable to allow traversing the valley within a single host's long-term infection. Recent studies have also highlighted the importance of considering the broader genotype space, which can reveal indirect paths that circumvent fitness valleys [105] , alternative genotypes that yield similar phenotypes [43] , and the costs imposed by deleterious mutants on higher mutation rates [106] .