Does a protein coevolve with its multiple interacting partners? A case study

Protein-protein interactions are playing a fundamental role in different cellular activities.  Although the coevolution of interacting protein pairs has been established by several groups, whether a protein having multiple interacting partners coevolves with all of its interacting partners or not have not been studied, so far. Here, the coevolution of proliferating cell nuclear antigen (PCNA) with their multiple interacting protein partners was studied. The ‘mirror tree’ method was used to predict the signature of coevolution of the interacting pairs.  The results show that PCNA, which interacts with a larger number of proteins, does not coevolve with each of its partners. Rather, the degree of coevolution varies in a statistically significant wider range. The nature of coevolution of these interacting pairs in two different lineages (archaea and eukarya) has been further investigated separately. Results show that the coordinated evolutions of some of the interacting pairs are different for two different lineages. The possible reasons (percentage of disorder region of partner proteins, synonymous to non-synonymous ratio, cascade interactions, etc.) of the variations have also been discussed.   Key words: Proliferating cell nuclear antigen (PCNA), coevolution, protein-protein interaction.