Fig 5. Discordant evolution of pairs of sites.

a. Discordant evolution of sites 754 and 858 in COX1 is likely explained by epistatic interaction. This is indicated by a deficit of consecutive substitutions together with clustering of non-consecutive substitutions, suggesting negative epistasis that is limited to substitutions at a subset of lineages. b. Discordant evolution of sites 334 and 353 in COX2 is likely explained by additive episodic selection. This is indicated by a deficit of consecutive substitutions together with repulsion of non-consecutive ones, suggesting alternating episodes of accelerated evolution at these two sites.