The Underlying Molecular and Network Level Mechanisms in the Evolution of Robustness in Gene Regulatory Networks

Mario Pujato, Thomas MacCarthy, Andras Fiser, Aviv Bergman

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Gene regulatory networks show robustness to perturbations. Previous works identified robustness as an emergent property of gene network evolution but the underlying molecular mechanisms are poorly understood. We used a multi-tier modeling approach that integrates molecular sequence and structure information with network architecture and population dynamics. Structural models of transcription factor-DNA complexes are used to estimate relative binding specificities. In this model, mutations in the DNA cause changes on two levels: (a) at the sequence level in individual binding sites (modulating binding specificity), and (b) at the network level (creating and destroying binding sites). We used this model to dissect the underlying mechanisms responsible for the evolution of robustness in gene regulatory networks. Results suggest that in sparse architectures (represented by short promoters), a mixture of local-sequence and network-architecture level changes are exploited. At the local-sequence level, robustness evolves by decreasing the probabilities of both the destruction of existent and generation of new binding sites. Meanwhile, in highly interconnected architectures (represented by long promoters), robustness evolves almost entirely via network level changes, deleting and creating binding sites that modify the network architecture.

Original languageEnglish (US)
Article numbere1002865
JournalPLoS Computational Biology
Volume9
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Gene Regulatory Networks
Gene Regulatory Network
Binding sites
binding sites
Genes
Network architecture
Binding Sites
Robustness
gene
Network Architecture
DNA
promoter regions
Promoter
Population dynamics
Specificity
Transcription factors
Information Services
Molecular Evolution
mutation
Structural Models

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Ecology
  • Molecular Biology
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Computational Theory and Mathematics

Cite this

The Underlying Molecular and Network Level Mechanisms in the Evolution of Robustness in Gene Regulatory Networks. / Pujato, Mario; MacCarthy, Thomas; Fiser, Andras; Bergman, Aviv.

In: PLoS Computational Biology, Vol. 9, No. 1, e1002865, 01.2013.

Research output: Contribution to journalArticle

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