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Functional organization and its implication in evolution of the human protein-protein interaction network.

Zhao Y, Mooney SD - BMC Genomics (2012)

Bottom Line: However, being able to capture topological properties does not necessarily mean it correctly reproduces how networks emerge and evolve.Consistently, we further found that the topological unit is also the functional unit of the network.Given our observations, we suggest that its significance should not be overlooked when studying network evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: Buck Institute for Research on Aging, Novato, California, USA.

ABSTRACT

Background: Based on the distinguishing properties of protein-protein interaction networks such as power-law degree distribution and modularity structure, several stochastic models for the evolution of these networks have been purposed, motivated by the idea that a validated model should reproduce similar topological properties of the empirical network. However, being able to capture topological properties does not necessarily mean it correctly reproduces how networks emerge and evolve. More importantly, there is already evidence suggesting functional organization and significance of these networks. The current stochastic models of evolution, however, grow the network without consideration for biological function and natural selection.

Results: To test whether protein interaction networks are functionally organized and their impacts on the evolution of these networks, we analyzed their evolution at both the topological and functional level. We find that the human network is shown to be functionally organized, and its function evolves with the topological properties of the network. Our analysis suggests that function most likely affects local modularity of the network. Consistently, we further found that the topological unit is also the functional unit of the network.

Conclusion: We have demonstrated functional organization of a protein interaction network. Given our observations, we suggest that its significance should not be overlooked when studying network evolution.

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Rate of change of network properties in different evolutionary stages. Rate of change of network properties in TG5-TG6 was not done because it could not be accurately estimated. Rate of change of network properties was normalized according to the overall changes for each network property for the purpose of comparison. (For rate of change of the network properties before normalization, see Additional file 1, Table S2.) TG: Temporal group.
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Figure 3: Rate of change of network properties in different evolutionary stages. Rate of change of network properties in TG5-TG6 was not done because it could not be accurately estimated. Rate of change of network properties was normalized according to the overall changes for each network property for the purpose of comparison. (For rate of change of the network properties before normalization, see Additional file 1, Table S2.) TG: Temporal group.

Mentions: Since network topologies vary among TGs, a question to ask is: "Is the change constant, or if not, in which evolutionary stage was the network topology changing the fastest?" For each temporal group, an approximate age (millions of years ago, Mya) is obtained based on previous molecular phylogenetic studies [33]. The rates of topological changes were measured by the differences in topological properties per unit of time. Under the neutral model without any functional significance, a constant rate of topological changes is expected. It is found, however, that during the stage from TG3 to TG4 the rate change in interaction degree, clustering coefficient and network distance were up to 10 times faster than other stages (Figure 3). By checking the major evolutionary events in this period, it suggests that TG3 to TG4 represents the evolution from cold-blooded animals to warm-blooded animals.


Functional organization and its implication in evolution of the human protein-protein interaction network.

Zhao Y, Mooney SD - BMC Genomics (2012)

Rate of change of network properties in different evolutionary stages. Rate of change of network properties in TG5-TG6 was not done because it could not be accurately estimated. Rate of change of network properties was normalized according to the overall changes for each network property for the purpose of comparison. (For rate of change of the network properties before normalization, see Additional file 1, Table S2.) TG: Temporal group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3375200&req=5

Figure 3: Rate of change of network properties in different evolutionary stages. Rate of change of network properties in TG5-TG6 was not done because it could not be accurately estimated. Rate of change of network properties was normalized according to the overall changes for each network property for the purpose of comparison. (For rate of change of the network properties before normalization, see Additional file 1, Table S2.) TG: Temporal group.
Mentions: Since network topologies vary among TGs, a question to ask is: "Is the change constant, or if not, in which evolutionary stage was the network topology changing the fastest?" For each temporal group, an approximate age (millions of years ago, Mya) is obtained based on previous molecular phylogenetic studies [33]. The rates of topological changes were measured by the differences in topological properties per unit of time. Under the neutral model without any functional significance, a constant rate of topological changes is expected. It is found, however, that during the stage from TG3 to TG4 the rate change in interaction degree, clustering coefficient and network distance were up to 10 times faster than other stages (Figure 3). By checking the major evolutionary events in this period, it suggests that TG3 to TG4 represents the evolution from cold-blooded animals to warm-blooded animals.

Bottom Line: However, being able to capture topological properties does not necessarily mean it correctly reproduces how networks emerge and evolve.Consistently, we further found that the topological unit is also the functional unit of the network.Given our observations, we suggest that its significance should not be overlooked when studying network evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: Buck Institute for Research on Aging, Novato, California, USA.

ABSTRACT

Background: Based on the distinguishing properties of protein-protein interaction networks such as power-law degree distribution and modularity structure, several stochastic models for the evolution of these networks have been purposed, motivated by the idea that a validated model should reproduce similar topological properties of the empirical network. However, being able to capture topological properties does not necessarily mean it correctly reproduces how networks emerge and evolve. More importantly, there is already evidence suggesting functional organization and significance of these networks. The current stochastic models of evolution, however, grow the network without consideration for biological function and natural selection.

Results: To test whether protein interaction networks are functionally organized and their impacts on the evolution of these networks, we analyzed their evolution at both the topological and functional level. We find that the human network is shown to be functionally organized, and its function evolves with the topological properties of the network. Our analysis suggests that function most likely affects local modularity of the network. Consistently, we further found that the topological unit is also the functional unit of the network.

Conclusion: We have demonstrated functional organization of a protein interaction network. Given our observations, we suggest that its significance should not be overlooked when studying network evolution.

Show MeSH