Linear motif-mediated interactions have contributed to the evolution of modularity in complex protein interaction networks

PLoS Comput Biol. 2014 Oct 9;10(10):e1003881. doi: 10.1371/journal.pcbi.1003881. eCollection 2014 Oct.


The modular architecture of protein-protein interaction (PPI) networks is evident in diverse species with a wide range of complexity. However, the molecular components that lead to the evolution of modularity in PPI networks have not been clearly identified. Here, we show that weak domain-linear motif interactions (DLIs) are more likely to connect different biological modules than strong domain-domain interactions (DDIs). This molecular division of labor is essential for the evolution of modularity in the complex PPI networks of diverse eukaryotic species. In particular, DLIs may compensate for the reduction in module boundaries that originate from increased connections between different modules in complex PPI networks. In addition, we show that the identification of biological modules can be greatly improved by including molecular characteristics of protein interactions. Our findings suggest that transient interactions have played a unique role in shaping the architecture and modularity of biological networks over the course of evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution*
  • Computational Biology / methods*
  • Humans
  • Mice
  • Models, Biological*
  • Protein Interaction Maps / physiology*
  • Protein Structure, Tertiary*

Grant support

This work was supported in part by Korean National Research Foundation grants (2013018606) and a POSTECH BSRI grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.