Phylogenomics of Orthologous Protein Families in Prokaryotes: Comparison of Evolutionary Profiles

Abstract

The sequence similarity relationships between the members of a protein family contain information on its evolutionary history, such as the relative time of horizontal transfer events, and the differential acceleration or deceleration of evolution in particular organisms in response to selective pressures. This paper presents a quantitative representation and comparison of evolutionary profiles of proteins, and finds correlations between evolutionary profile similarities and evolutionary or functional links between proteins. Using a dataset of 84 orthologous protein families ubiquitous in prokaryotes, we obtain the evolutionary profile of each family as a vector of inter-sequence distances. We then compare the family-specific evolutionary vectors and quantitate the evolutionary similarity between families. Two primary methods for vector comparison were used, namely the angle between vectors and correlation distance between vectors. Both approaches are powerful enough to recognize known evolutionary similarities, and yield similar inter-family relationships, but they also display important differences. These differences are shown to exist because the two methods recognize different aspects of the evolutionary profile. The inter-vector angle is an effective measure of the difference in the overall form of phylogenetic trees even in cases where the topology of the tree is not well-defined, whereas the correlation distance is especially effective in recognizing similarities in topology. When the protein families are clustered based on either the angle or the correlation distance between them, the cluster dendrogram shows a core cluster consisting of ancient protein families with the standard phylogeny. In addition, evolutionary profile comparison also detects plausible evolutionary similarities between unannotated proteins and proteins of known function. For instance, the bacterial yjeF gene and the ygjD/ydiE gene are both predicted to be involved in cell envelope biogenesis. In summary, we describe quantitative comparisons of protein family specific evolutionary profiles, and illustrate their power in detecting broader evolutionary trends and specific functional relationships between proteins. Keywords: Comparative bioinformatics, functional motifs, phylogenetic methods, prokaryotic evolution, sequence profiles.