Evolution of protein-protein interaction networks in yeast

Abstract

Interest in the evolution of protein-protein and genetic interaction networks has been rising in recent years, but the lack of large-scale high quality comparative datasets has acted as a barrier. Here, we carried out a comparative analysis of computationally predicted protein-protein interaction (PPI) networks from five closely related yeast species. We used the Protein-protein Interaction Prediction Engine (PIPE), which uses a database of known interactions to make sequence-based PPI predictions, to generate high quality predicted interactomes. Simulated proteomes and corresponding PPI networks were used to provide null expectations for the extent and nature of PPI network evolution. We found strong evidence for conservation of PPIs, with lower than expected levels of change in PPIs for about a quarter of the proteome. Furthermore, we found that changes in predicted PPI networks are poorly predicted by sequence divergence. Our analyses identified a number of functional classes experiencing fewer PPI changes than expected, suggestive of purifying selection on PPIs. Our results demonstrate the added benefit of considering predicted PPI networks when studying the evolution of closely related organisms.

Fig 1. An overview of the computational process used to infer PPI networks for each of the 5 yeast species, and to generate the simulated null model.

Molecular evolutionary parameters were inferred under the M0 model in PAML, and were used to generate simulated datasets using INDELible. PIPE was used to infer PPI networks for both the real and simulated datasets.

Fig 2. Phylogeny of the five yeast species studied here.

Fig 3. Distribution of the change in protein-protein interaction across the phylogeny.

The distribution of γ, which represents the total number of interaction changes (gains or losses) over the entire phylogeny. The majority of proteins experience relatively few changes in interaction across the phylogeny with a small number of proteins experiencing many changes.

Fig 4. Comparing the change in protein-protein interaction to protein degree and rate of sequence change across the phylogeny.

Comparison of changes in PPIs across the phylogeny (γ) to degree (A) or to rate of substitution across the phylogeny (ω) (B). A protein’s γ is correlated with its degree in the network (see regression line in panel A), but not with its overall rate of substitution.

Fig 5. Proteins which experience a lower or higher number of changes in PPIs in the real data compared to the simulated interactomes.

Proteins which experience a lower (A) or higher (B) number of changes in inferred PPIs in the real data in comparison to the simulated interactomes. Each protein’s real γ is plotted in red and the range of γ observed in the null model are plotted in black.