RT Journal Article SR Electronic T1 Linking influenza virus evolution within and between human hosts JF bioRxiv FD Cold Spring Harbor Laboratory SP 812016 DO 10.1101/812016 A1 Katherine S. Xue A1 Jesse D. Bloom YR 2019 UL http://biorxiv.org/content/early/2019/10/21/812016.abstract AB Influenza viruses rapidly diversify within individual human infections. Several recent studies have deep-sequenced clinical influenza infections to identify viral variation within hosts, but it remains unclear how within-host mutations fare in the global viral population. Here, we compare viral variation within and between hosts to link influenza’s evolutionary dynamics across scales. Synonymous sites evolve at similar rates at both scales, indicating that global evolution at these putatively neutral sites results from the accumulation of within-host variation. However, nonsynonymous mutations are depleted in global viral populations compared to within hosts, suggesting that selection purges many of the protein-altering changes that arise within hosts. The exception is at antigenic sites, where selection detectably favors nonsynonymous mutations at the global scale, but not within hosts. These results suggest that selection against deleterious mutations and selection for antigenic change are the main forces that transform influenza’s within-host genetic variation into global evolution.