ArticlePLoS computational biology2013
The underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Evolution enhances mutational robustness and suppresses the emergence of a new phenotype: A new computational approach for studying evolution.PLoS computational biology · 2022Article
- Emergence of cooperative bistability and robustness of gene regulatory networks.PLoS computational biology · 2020Article
- miR-302b-3p Promotes Self-Renewal Properties in Leukemia Inhibitory Factor-Withdrawn Embryonic Stem Cells.Cell journal · 2018Article
- The essentiality of non-coding RNAs in cell reprogramming.Non-coding RNA research · 2017Review
- Potential for evolution of complex defense strategies in a multi-scale model of virus-host coevolution.BMC evolutionary biology · 2016Article
- What does it take to evolve an enhancer? A simulation-based study of factors influencing the emergence of combinatorial regulation.Genome biology and evolution · 2015Article
- Prediction of DNA binding motifs from 3D models of transcription factors; identifying TLX3 regulated genes.Nucleic acids research · 2014Article
- SoxNeuro orchestrates central nervous system specification and differentiation in Drosophila and is only partially redundant with Dichaete.Genome biology · 2014Article
- Latent phenotypes pervade gene regulatory circuits.BMC systems biology · 2014Article
- Simulations of enhancer evolution provide mechanistic insights into gene regulation.Molecular biology and evolution · 2014Article
- Exploring the mechanisms of differentiation, dedifferentiation, reprogramming and transdifferentiation.PloS one · 2014Article
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Authors and funding
4 authors.
Funding
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.
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