Bacterial Protein Interaction Networks: Connectivity is Ruled by Gene Conservation, Essentiality and Function

Abstract

Background: Protein-protein interaction (PPI) networks are the backbone of all processes in living cells. In this work, we relate conservation, essentiality and functional repertoire of a gene to the connectivity k (i.e. the number of interactions, links) of the corresponding protein in the PPI network. Methods: On a set of 42 bacterial genomes of different sizes, and with reasonably separated evolutionary trajectories, we investigate three issues: i) whether the distribution of connectivities changes between PPI subnetworks of essential and nonessential genes; ii) how gene conservation, measured both by the evolutionary retention index (ERI) and by evolutionary pressures, is related to the connectivity of the corresponding protein; iii) how PPI connectivities are modulated by evolutionary and functional relationships, as represented by the Clusters of Orthologous Genes (COGs). Conclusion: We show that conservation, essentiality and functional specialisation of genes constrain the connectivity of the corresponding proteins in bacterial PPI networks. In particular, we isolated a core of highly connected proteins (connectivities k≥40), which is ubiquitous among the species considered here, though mostly visible in the degree distributions of bacteria with small genomes (less than 1000 genes). Conclusion: The genes that support this highly connected core are conserved, essential and, in most cases, belong to the COG cluster J, related to ribosomal functions and the processing of genetic information.