Fig. 1

Potential interface substitutions that may maintain or alter a physical interaction and the evolutionary consequences for the protein-protein interaction network. In this hypothetical case an arginine (ARG) makes a physical interaction with a phenylalanine (PHE) at a binding interface enabling a physical interaction (a). The substitution of an ARG to a PHE may preserve the physical interaction if the PHE can still contact the interacting residue across the binding interface (b). However substitutions to amino acids that can no longer contact the interacting residue (or chain) because they cannot bridge the interface (c) or are orientated away from the interface (d) may result in an alteration of the physical interaction. In a–d protein backbones are shown in grey and blue with residue side-chain in red, purple and yellow. Yellow and red dots indicate a physical contact between residues. Changes in physical interactions have several potential consequences for the protein-protein interaction network. If we consider the case of a duplication event (red nodes in e, f and g), immediately after duplication the duplicate interfaces will be identical and all physical interactions will be maintained (e). Selection may favour this scenario (dosage benefit) and changes in interfaces may be constrained to maintain the interactions. Alternatively, substitutions in interfaces may lead to a divergence of interactions between the duplicates (subfunctionalisation - f). It is also possible, in rare cases, that divergence in binding interfaces may result in the formation of novel physical interactions (neofunctionalisation - g). In the network diagrams blue nodes represent proteins, red nodes duplicate proteins and edges between nodes depict physical interactions