Specificity and Evolvability in Eukaryotic Protein Interaction Networks

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Abstract
Progress in uncovering the protein interaction networks of several species has led to questions of what underlying principles might govern their organization. Few studies have tried to determine the impact of protein interaction network evolution on the observed physiological differences between species. Using comparative genomics and structural information, we show here that eukaryotic species have rewired their interactomes at a fast rate of approximately 10−5 interactions changed per protein pair, per million years of divergence. For Homo sapiens this corresponds to 103 interactions changed per million years. Additionally we find that the specificity of binding strongly determines the interaction turnover and that different biological processes show significantly different link dynamics. In particular, human proteins involved in immune response, transport, and establishment of localization show signs of positive selection for change of interactions. Our analysis suggests that a small degree of molecular divergence can give rise to important changes at the network level. We propose that the power law distribution observed in protein interaction networks could be partly explained by the cell's requirement for different degrees of protein binding specificity. To understand how the cell performs the required biological functions and reacts to changes in the environment, scientists have been studying how cellular components interact. In recent years, new experimental methods have immensely increased our ability to map out these connections. However, it is important to keep in mind that biological systems are constantly evolving to cope with environmental changes. What then is the impact of the genomic variability brought by point mutations, segmental duplications, etc., on these interaction networks? We have tried here to quantify the rate by which protein interactions changed during the evolution of eukaryotic cells. According to the authors, about 0.5% to 3% of the interactions can change every million years. Also, protein properties, such as binding specificity (defined as the number of binding surfaces or binding partners) and protein function, help determine the rate of interaction turnover. This work suggests that protein interactions are evolutionarily plastic and the fact that a group of proteins has been conserved in different genomes does not mean that their interaction repertoire and functions are necessarily conserved. This work emphasizes the importance of studying biological systems in the context of evolutionary change.