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Evolution of biomolecular networks — lessons from metabolic and protein interactions

Key Points

  • Biomolecular networks, such as protein–protein interaction (PPI) or metabolic networks, organize the 'parts lists' generated by various large-scale approaches and are therefore frameworks that facilitate many discoveries in molecular biology. Nodes represent proteins (specifically enzymes in metabolic networks), whereas PPIs in PPI networks and enzyme–enzyme interactions through shared metabolites in metabolic networks are considered as links.

  • Using this framework, general knowledge on the topology of networks can be applied. However, specification of biomolecular networks, such as the impact of the environment and experimental conditions, also have to be taken into account. The experimental conditions raise important issues regarding the accuracy and coverage of these networks, which also have an impact on the conclusions about the evolution of the networks.

  • The evolutionary dynamics of PPI and metabolic networks is mostly based on two classes of genetic events. The first is duplication and loss of regions encompassing complete genes, which implies the addition and loss of nodes and links. The second is more fine-tuned and includes point mutations, small insertions or deletions, and mutations that affect the regulation of genes, which implies the addition and loss of links.

  • Owing to different biological functions and distinct topological features of PPI and metabolic networks, changes of nodes and links in each are subject to different selection.

  • So far, most of the research on networks is devoted to in vitro and static networks, and these are usually considered in two dimensions (2D networks) — that is, without spatial (3D) or temporal (4D) resolution. Many network features and their evolution can be understood only when taking spatiotemporal resolution into account.

Abstract

Despite only becoming popular at the beginning of this decade, biomolecular networks are now frameworks that facilitate many discoveries in molecular biology. The nodes of these networks are usually proteins (specifically enzymes in metabolic networks), whereas the links (or edges) are their interactions with other molecules. These networks are made up of protein–protein interactions or enzyme–enzyme interactions through shared metabolites in the case of metabolic networks. Evolutionary analysis has revealed that changes in the nodes and links in protein–protein interaction and metabolic networks are subject to different selection pressures owing to distinct topological features. However, many evolutionary constraints can be uncovered only if temporal and spatial aspects are included in the network analysis.

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Figure 1: Components of biomolecular networks and their accumulation over time.
Figure 2: Network rewiring in S. pombe and S. cerevisiae.
Figure 3: Topologies of PPI and metabolic networks in yeast and E. coli.
Figure 4: Metabolic dynamics during the yeast cell cycle.

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Acknowledgements

The authors thank V. van Noort for supporting statistical analysis of the network, J. Muller for supporting gene annotation procedures and all members of the Bork group for critical discussions. The work in the author's laboratory is supported by the BMBF grant Neuronet (17282) and the EU grant Metahit (17286).

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41580_2009_BFnrm2787_MOESM3_ESM.pdf

Supplementary information S1 (box) | Data coverage of interaction networks for selected studies and resources (PDF 577 kb)

Supplementary information S2 (Box) | Accuracy issues in comparative network analysis (PDF 266 kb)

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Glossary

Graph theory

The study of the properties of graphs. A graph is a mathematical structure used to model the pairwise relationships between objects. It is composed of a collection of nodes (vertices) and links (edges).

TAP–MS

A method used to detect physical protein–protein interactions by a series of affinity column purifications, followed by mass spectrometry for their identification.

Protein fragment complementation assay

A method used to measure protein–protein physical interactions. Protein interactions are coupled to the refolding of β-lactamase, which is fragmented and each of the two fragments is fused to the two proteins of interest. The reconstitution of β-lactamase activity acts as an interaction detector.

Power law

A statistical model that describes that one quantity is proportional to the power of another quantity.

Triosephosphate isomerase (TIM)-barrel fold

The most frequent and conserved protein fold, comprising eight α-helices and eight β-sheets.

Orthologue

A gene present in different species that evolved from a common ancestral gene by speciation.

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Yamada, T., Bork, P. Evolution of biomolecular networks — lessons from metabolic and protein interactions. Nat Rev Mol Cell Biol 10, 791–803 (2009). https://doi.org/10.1038/nrm2787

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