Gene duplications contribute to the overrepresentation of interactions between proteins of a similar age

Abstract Background The study of biological networks and how they have evolved is fundamental to our understanding of the cell. By investigating how proteins of different ages are connected in the protein interaction network, one can infer how that network has expanded in evolution, without the need for explicit reconstruction of ancestral networks. Studies that implement this approach show that proteins are often connected to proteins of a similar age, suggesting a simultaneous emergence of interacting proteins. There are several theories explaining this phenomenon, but despite the importance of gene duplication in genome evolution, none consider protein family dynamics as a contributing factor. Results In an S. cerevisiae protein interaction network we investigate to what extent edges that arise from duplication events contribute to the observed tendency to interact with proteins of a similar age. We find that part of this tendency is explained by interactions between paralogs. Age is usually defined on the level of protein families, rather than individual proteins, hence paralogs have the same age. The major contribution however, is from interaction partners that are shared between paralogs. These interactions have most likely been conserved after a duplication event. To investigate to what extent a nearly neutral process of network growth can explain these results, we adjust a well-studied network growth model to incorporate protein families. Our model shows that the number of edges between paralogs can be amplified by subsequent duplication events, thus explaining the overrepresentation of interparalog edges in the data. The fact that interaction partners shared by paralogs are often of the same age as the paralogs does not arise naturally from our model and needs further investigation. Conclusion We amend previous theories that explain why proteins of a similar age prefer to interact by demonstrating that this observation can be partially explained by gene duplication events. There is an ongoing debate on whether the protein interaction network is predominantly shaped by duplication and subfunctionalization or whether network rewiring is most important. Our analyses of S. cerevisiae protein interaction networks demonstrate that duplications have influenced at least one property of the protein interaction network: how proteins of different ages are connected.