Covariation of Branch Lengths in Phylogenies of Functionally Related Genes

Recent studies have shown evidence for the coevolution of functionally-related genes. This coevolution is a result of constraints to maintain functional relationships between interacting proteins. The studies have focused on the correlation in gene tree branch lengths of proteins that are directly interacting with each other. We here hypothesize that the correlation in branch lengths is not limited only to proteins that directly interact, but also to proteins that operate within the same pathway. Using generalized linear models as a basis of identifying correlation, we attempted to predict the gene ontology (GO) terms of a gene based on its gene tree branch lengths. We applied our method to a dataset consisting of proteins from ten prokaryotic species. We found that the degree of accuracy to which we could predict the function of the proteins from their gene tree varied substantially with different GO terms. In particular, our model could accurately predict genes involved in translation and certain ribosomal activities with the area of the receiver-operator curve of up to 92%. Further analysis showed that the similarity between the trees of genes labeled with similar GO terms was not limited to genes that physically interacted, but also extended to genes functioning within the same pathway. We discuss the relevance of our findings as it relates to the use of phylogenetic methods in comparative genomics.