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Comparative Study
. 2003 May 23:3:11.
doi: 10.1186/1471-2148-3-11. Epub 2003 May 23.

A simple dependence between protein evolution rate and the number of protein-protein interactions

Hunter B Fraser  1 , Dennis P Wall, Aaron E Hirsh
Affiliations
Comparative Study

A simple dependence between protein evolution rate and the number of protein-protein interactions

Hunter B Fraser et al. BMC Evol Biol. .

Abstract

Background: It has been shown for an evolutionarily distant genomic comparison that the number of protein-protein interactions a protein has correlates negatively with their rates of evolution. However, the generality of this observation has recently been challenged. Here we examine the problem using protein-protein interaction data from the yeast Saccharomyces cerevisiae and genome sequences from two other yeast species.

Results: In contrast to a previous study that used an incomplete set of protein-protein interactions, we observed a highly significant correlation between number of interactions and evolutionary distance to either Candida albicans or Schizosaccharomyces pombe. This study differs from the previous one in that it includes all known protein interactions from S. cerevisiae, and a larger set of protein evolutionary rates. In both evolutionary comparisons, a simple monotonic relationship was found across the entire range of the number of protein-protein interactions. In agreement with our earlier findings, this relationship cannot be explained by the fact that proteins with many interactions tend to be important to yeast. The generality of these correlations in other kingdoms of life unfortunately cannot be addressed at this time, due to the incompleteness of protein-protein interaction data from organisms other than S. cerevisiae.

Conclusions: Protein-protein interactions tend to slow the rate at which proteins evolve. This may be due to structural constraints that must be met to maintain interactions, but more work is needed to definitively establish the mechanism(s) behind the correlations we have observed.

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Figures

Figure 1
Figure 1
The relationship between number of protein-protein interactions and evolutionary rate between S. cerevisiae and S. pombe. (a) The relationship between number of protein-protein interactions and evolutionary rate for all 2119 orthologs with protein interaction data. Several outliers are not shown but were included in the analysis. (b) Average evolutionary rates of genes binned by their number of protein-protein interactions.
Figure 2
Figure 2
The relationship between number of protein-protein interactions and evolutionary rates between S. cerevisiae and C. albicans. (a) The relationship between number of protein-protein interactions and evolutionary rate for all 2496 orthologs with protein interaction data. Several outliers are not shown but were included in the analysis. (b) Average evolutionary rates of genes binned by their number of protein-protein interactions.
Figure 3
Figure 3
Testing the different lists of protein-protein interactions and evolutionary rates from the two studies. (a) A significant correlation is found when using evolutionary rates of orthologs from Jordan et al. [4] with our list of protein-protein interactions. Several outliers are not shown but were included in the analysis. (b) No correlation is seen when using our evolutionary rates of orthologs with Jordan et al.'s list of protein-protein interactions.
Figure 4
Figure 4
Diagram of correlations between number of protein-protein interactions, evolutionary rates, and fitness effects (a) Each arrow represents the correlation between the two variables it connects. Whether or not the correlation is statistically significant by Kendall's Partial Tau is shown by the P-values next to each arrow in (b) and (c). (b) The significance of each correlation for the S. cerevisiae-S. pombe comparison. Note that the arrow connecting number of protein-protein interactions and evolutionary rates is highly significant, with none of the 105 randomizations of the data having a stronger correlation. (c) The significance of each correlation for the S. cerevisiae–C. albicans comparison. Note that the arrow connecting number of protein-protein interactions and evolutionary rates is highly significant, with none of the 105 randomizations of the data having a stronger correlation.
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References

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