Fig. 3.

Phylogenetic tree of neuraminidase (NA) subtype N1 illustrating a putatively epistatic interaction. The same tree from Fig. 2 is used to illustrate the methodology presented in Kryazhimskiy et al. (2011). Nonresistant branches with the D344N mutation are coloured in blue. Branches with the H274Y resistance mutation are coloured in red. The phylogeny suggests an epistatic interaction between sites 344 and 275 where the H274Y substitution at site 275 (site 274 in N2 numbering scheme) appears multiple times immediately following the D344N substitution at site 344 (shaded in blue). This co-occurrence is consistent with the idea that the substitution at site 344 acts as a ‘permissive’ mutation and that these mutations interact in a positively epistatic manner.