Example of putative inter-gene epistasis between sites N2-126 and H3-63 and H3-81.

<p>Mutations at sites N2-126 and glycosylation motifs starting at sites H3-63 and H3-81 are marked by orange, blue and green circles, respectively. All three mutations affecting the H3-63 glycosylation motif occurred at site H3-63 and created a new glycosylation site. Two mutations affecting the H3-81 glycosylation motif occurred at site H3-81 and one occurred at site H3-83, but all of them destroyed an existing glycosylation motif. Only mutations that form consecutive pairs are shown (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005404#sec015" target="_blank">Materials and Methods</a>); see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005404#pgen.1005404.s013" target="_blank">S3 Data</a> for all mutations. Vertical bars show years in which the isolates where sampled. The inset shows the inferred directionality of epistatic interactions with arrows pointing from the leading to the trailing site.