Trees on networks: resolving statistical patterns of phylogenetic similarities among interacting proteins

BACKGROUND: Phylogenies capture the evolutionary ancestry linking extant species. Correlations and similarities among a set of species are mediated by and need to be understood in terms of the phylogenic tree. In a similar way it has been argued that biological networks also induce correlations among sets of interacting genes or their protein products. RESULTS: We develop suitable statistical resampling schemes that can incorporate these two potential sources of correlation into a single inferential framework. To illustrate our approach we apply it to protein interaction data in yeast and investigate whether the phylogenetic trees of interacting proteins in a panel of yeast species are more similar than would be expected by chance. CONCLUSIONS: While we find only negligible evidence for such increased levels of similarities, our statistical approach allows us to resolve the previously reported contradictory results on the levels of co-evolution induced by protein-protein interactions. We conclude with a discussion as to how we may employ the statistical framework developed here in further functional and evolutionary analyses of biological networks and systems.