The underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.

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 inf...

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Autores principales:	Mario Pujato, Thomas MacCarthy, Andras Fiser, Aviv Bergman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5a05764402374b44bef1cbaa79ffa518
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spelling	oai:doaj.org-article:5a05764402374b44bef1cbaa79ffa5182021-11-18T05:52:33ZThe underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.1553-734X1553-735810.1371/journal.pcbi.1002865https://doaj.org/article/5a05764402374b44bef1cbaa79ffa5182013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300434/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Gene 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.Mario PujatoThomas MacCarthyAndras FiserAviv BergmanPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 1, p e1002865 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Mario Pujato Thomas MacCarthy Andras Fiser Aviv Bergman The underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.
description	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.
format	article
author	Mario Pujato Thomas MacCarthy Andras Fiser Aviv Bergman
author_facet	Mario Pujato Thomas MacCarthy Andras Fiser Aviv Bergman
author_sort	Mario Pujato
title	The underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.
title_short	The underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.
title_full	The underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.
title_fullStr	The underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.
title_full_unstemmed	The underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.
title_sort	underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/5a05764402374b44bef1cbaa79ffa518
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The underlying molecular and network level mechanisms in the evolution of robustness in gene regulatory networks.

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