Email updates

Keep up to date with the latest news and content from BMC Evolutionary Biology and BioMed Central.

Open Access Research article

The origins of the evolutionary signal used to predict protein-protein interactions

Lakshmipuram S Swapna1, Narayanaswamy Srinivasan1, David L Robertson2 and Simon C Lovell2*

Author affiliations

1 Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India

2 Computational and Evolutionary Biology, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK

For all author emails, please log on.

Citation and License

BMC Evolutionary Biology 2012, 12:238  doi:10.1186/1471-2148-12-238

Published: 6 December 2012



The correlation of genetic distances between pairs of protein sequence alignments has been used to infer protein-protein interactions. It has been suggested that these correlations are based on the signal of co-evolution between interacting proteins. However, although mutations in different proteins associated with maintaining an interaction clearly occur (particularly in binding interfaces and neighbourhoods), many other factors contribute to correlated rates of sequence evolution. Proteins in the same genome are usually linked by shared evolutionary history and so it would be expected that there would be topological similarities in their phylogenetic trees, whether they are interacting or not. For this reason the underlying species tree is often corrected for. Moreover processes such as expression level, are known to effect evolutionary rates. However, it has been argued that the correlated rates of evolution used to predict protein interaction explicitly includes shared evolutionary history; here we test this hypothesis.


In order to identify the evolutionary mechanisms giving rise to the correlations between interaction proteins, we use phylogenetic methods to distinguish similarities in tree topologies from similarities in genetic distances. We use a range of datasets of interacting and non-interacting proteins from Saccharomyces cerevisiae. We find that the signal of correlated evolution between interacting proteins is predominantly a result of shared evolutionary rates, rather than similarities in tree topology, independent of evolutionary divergence.


Since interacting proteins do not have tree topologies that are more similar than the control group of non-interacting proteins, it is likely that coevolution does not contribute much to, if any, of the observed correlations.

Co-evolution; Correlated evolution; Protein evolution; Phylogenetic; Protein-protein complexes; Protein-protein interactions