Distribution of essential interactions in model gene regulatory networks under mutation-selection balance

Phys Rev E Stat Nonlin Soft Matter Phys. 2010 Jul;82(1 Pt 1):011908. doi: 10.1103/PhysRevE.82.011908. Epub 2010 Jul 14.

Abstract

Gene regulatory networks typically have low in-degrees, whereby any given gene is regulated by few of the genes in the network. They also tend to have broad distributions for the out-degree. What mechanisms might be responsible for these degree distributions? Starting with an accepted framework of the binding of transcription factors to DNA, we consider a simple model of gene regulatory dynamics. There, we show that selection for a target expression pattern leads to the emergence of minimum connectivities compatible with the selective constraint. As a consequence, these gene networks have low in-degree and "functionality" is parsimonious, i.e., is concentrated on a sparse number of interactions as measured for instance by their essentiality. Furthermore, we find that mutations of the transcription factors drive the networks to have broad out-degrees. Finally, these classes of models are evolvable, i.e., significantly different genotypes can emerge gradually under mutation-selection balance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computer Simulation
  • Gene Expression Regulation / genetics*
  • Humans
  • Models, Genetic*
  • Mutation / genetics*
  • Proteome / genetics*
  • Selection, Genetic / genetics*
  • Signal Transduction / genetics*

Substances

  • Proteome