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Evolution of protein-protein interaction networks in yeast

View Article: PubMed Central - PubMed

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 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.

No MeSH data available.


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  model are plotted in                            black.
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pone.0171920.g005: 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 model are plotted in black.

Mentions: Proteins whose interactions are conserved were identified as those whose γ in the real dataset falls below γ in all of the 100 simulated datasets (for P < 0.01). Here, the simulated datasets provide a distribution for inferred changes in PPIs owing to mutation alone; these changes will reflect both true losses or gains of interactions, and false positives—i.e., changes inferred by PIPE that do not reflect true changes. A reduced true γ in comparison to the simulated datasets provides evidence that natural selection maintains PPIs by selecting against interaction-altering mutations. 936 proteins—almost a quarter of the proteome—were identified by this criterion (Fig 5A).


Evolution of protein-protein interaction networks in yeast
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  model are plotted in                            black.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382968&req=5

pone.0171920.g005: 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 model are plotted in black.
Mentions: Proteins whose interactions are conserved were identified as those whose γ in the real dataset falls below γ in all of the 100 simulated datasets (for P < 0.01). Here, the simulated datasets provide a distribution for inferred changes in PPIs owing to mutation alone; these changes will reflect both true losses or gains of interactions, and false positives—i.e., changes inferred by PIPE that do not reflect true changes. A reduced true γ in comparison to the simulated datasets provides evidence that natural selection maintains PPIs by selecting against interaction-altering mutations. 936 proteins—almost a quarter of the proteome—were identified by this criterion (Fig 5A).

View Article: PubMed Central - PubMed

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 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.

No MeSH data available.