Abstract

BackgroundHigh-throughput screens have revealed large-scale protein interaction networks defining most cellular functions. How the proteins were added to the protein interaction network during its growth is a basic and important issue. Network motifs represent the simplest building blocks of cellular machines and are of biological significance.ResultsHere we study the evolution of protein interaction networks from the perspective of network motifs. We find that in current protein interaction networks, proteins of the same age class tend to form motifs and such co-origins of motif constituents are affected by their topologies and biological functions. Further, we find that the proteins within motifs whose constituents are of the same age class tend to be densely interconnected, co-evolve and share the same biological functions, and these motifs tend to be within protein complexes.ConclusionsOur findings provide novel evidence for the hypothesis of the additions of clustered interacting nodes and point out network motifs, especially the motifs with the dense topology and specific function may play important roles during this process. Our results suggest functional constraints may be the underlying driving force for such additions of clustered interacting nodes.

Highlights

  • High-throughput screens have revealed large-scale protein interaction networks defining most cellular functions

  • The tendency between proteins of the same/different age classes to form motifs To understand the evolutionary history of protein interaction network (PIN) from the network motif perspective, we first analyze the tendency between proteins of the same/different age classes to form motifs in the PIN

  • For the research on the growth of PINs, it is improper to assign the original age of all proteins derived from the direct or indirect duplication of a common traceable earliest ancestral protein to the time when the traceable earliest ancestor emerged, because new proteins directly or indirectly from the ancestor are continuously produced at various stages during the evolution of PINs after this ancestor was created

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Summary

Introduction

High-throughput screens have revealed large-scale protein interaction networks defining most cellular functions. Previous studies on the evolution of PINs focus either on the individual protein level [11,17,18,19,20,21,22,23,24,25,26,27], interaction level [11,14,28,29,30], functional module level [9,15,31,32,33,34,35,36,37] or the whole network level [2,3,4,5,6,7,8,10,13,16]. Compared with functional modules [41], owing to the definite definition of motifs, they can be explicitly identified and enumerated in various cellular networks [40]

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