The integrity of the yeast protein-protein interaction network is maintained by a few highly connected proteins, or hubs, which hold the numerous less-connected proteins together. The structural importance and the increased essentiality of these proteins suggest that they are likely to be conserved in evolution, implying a strong relationship between the number of interactions and their evolutionary distance to its orthologs in other organisms. The existence of this coherence was recently reported to strongly depend on the quality of the protein interaction and orthologs data. Here, we introduce a novel method, the evolutionary excess retention (ER), allowing us to uncover a robust and strong correlation between the conservation, essentiality, and connectivity of a yeast protein. We conclude that the relevance of the hubs for the network integrity is simultaneously reflected by a considerable probability of simultaneously being evolutionarily conserved and essential, an observation that does not have an equivalent for nonessential proteins. Providing a thorough assessment of the impact noisy and incomplete data have on our findings, we conclude that our results are largely insensitive to the quality of the utilized data.
Copyright 2004 Cold Spring Harbor Laboratory Press ISSN