No simple dependence between protein evolution rate and the number of protein-protein interactions: only the most prolific interactors tend to evolve slowly

I King Jordan,Eugene V Koonin,Yuri I Wolf

doi:10.1186/1471-2148-3-1

Abstract

BackgroundIt has been suggested that rates of protein evolution are influenced, to a great extent, by the proportion of amino acid residues that are directly involved in protein function. In agreement with this hypothesis, recent work has shown a negative correlation between evolutionary rates and the number of protein-protein interactions. However, the extent to which the number of protein-protein interactions influences evolutionary rates remains unclear. Here, we address this question at several different levels of evolutionary relatedness.ResultsManually curated data on the number of protein-protein interactions among Saccharomyces cerevisiae proteins was examined for possible correlation with evolutionary rates between S. cerevisiae and Schizosaccharomyces pombe orthologs. Only a very weak negative correlation between the number of interactions and evolutionary rate of a protein was observed. Furthermore, no relationship was found between a more general measure of the evolutionary conservation of S. cerevisiae proteins, based on the taxonomic distribution of their homologs, and the number of protein-protein interactions. However, when the proteins from yeast were assorted into discrete bins according to the number of interactions, it turned out that 6.5% of the proteins with the greatest number of interactions evolved, on average, significantly slower than the rest of the proteins. Comparisons were also performed using protein-protein interaction data obtained with high-throughput analysis of Helicobacter pylori proteins. No convincing relationship between the number of protein-protein interactions and evolutionary rates was detected, either for comparisons of orthologs from two completely sequenced H. pylori strains or for comparisons of H. pylori and Campylobacter jejuni orthologs, even when the proteins were classified into bins by the number of interactions.ConclusionThe currently available comparative-genomic data do not support the hypothesis that the evolutionary rates of the majority of proteins substantially depend on the number of protein-protein interactions they are involved in. However, a small fraction of yeast proteins with the largest number of interactions (the hubs of the interaction network) tend to evolve slower than the bulk of the proteins.

Highlights

It has been suggested that rates of protein evolution are influenced, to a great extent, by the proportion of amino acid residues that are directly involved in protein function
Consistent with this prediction, a negative correlation has been reported between protein evolutionary rates, which were determined from evolutionary distances between orthologous proteins from yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans, and the number of protein-protein interactions proteins are involved in [4]
Evolutionary rates and protein-protein interactions: yeast A total of 1,879 pairs of orthologous proteins, one from S. cerevisiae and one from S. pombe, were identified, and for 1,004 of these, there was data on protein-protein interactions of the S. cerevisiae member in the Munich Information Center for Protein Sequences (MIPS) database [5]. For these 1,004 orthologous pairs, the number of protein-protein interactions detected for the S. cerevisiae protein was plotted against the calculated substitution rates between orthologs (Figure 1a)

Summary

Introduction

It has been suggested that rates of protein evolution are influenced, to a great extent, by the proportion of amino acid residues that are directly involved in protein function. It has been suggested that proteins' evolutionary rates are determined by the proportion of amino-acids that are critical to their function [3] According to this intuitively plausible notion, proteins with a greater fraction of amino acid residues that play an essential role in the protein's function are predicted to evolve slower than those with a smaller fraction of such crucial residues. Consistent with this prediction, a negative correlation has been reported between protein evolutionary rates, which were determined from evolutionary distances between orthologous proteins from yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans, and the number of protein-protein interactions (i.e., physical interactions determined, primarily, using the yeast two-hybrid system) proteins are involved in [4]. We sought to further investigate this phenomenon by examining the relationship between the number of proteinprotein interacting partners and protein evolutionary rates for the yeasts S. cerevisiae and Schizosaccharomyces pombe as well as for the proteobacteria Helicobacter pylori and Camplyobacter jejuni

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Results

Discussion

Conclusion