Example of putative inter-gene epistasis between sites H1-222 and N1-274.

<p>Mutations at sites H1-222 and N1-274 are marked by orange and blue circles, respectively; mutations at site N1-275 are marked by green circles. Site N1-275 was found to form a highly scoring inter-gene epistatic pair with site N1-274 in our previous study [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005404#pgen.1005404.ref021" target="_blank">21</a>] (see text for details). 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.s012" target="_blank">S2 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.