Regulatory network structure as a dominant determinant of transcription factor evolutionary rate.

The evolution of transcriptional regulatory networks has thus far mostly been studied at the level of cis-regulatory elements. To gain a complete understanding of regulatory network evolution we must also study the evolutionary role of trans-factors, such as transcription factors (TFs). Here, we sys...

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Autores principales:	Jasmin Coulombe-Huntington, Yu Xia
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/acbd43732153438692f9ec6ef91de5a1
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spelling	oai:doaj.org-article:acbd43732153438692f9ec6ef91de5a12021-11-18T05:52:47ZRegulatory network structure as a dominant determinant of transcription factor evolutionary rate.1553-734X1553-735810.1371/journal.pcbi.1002734https://doaj.org/article/acbd43732153438692f9ec6ef91de5a12012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23093926/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The evolution of transcriptional regulatory networks has thus far mostly been studied at the level of cis-regulatory elements. To gain a complete understanding of regulatory network evolution we must also study the evolutionary role of trans-factors, such as transcription factors (TFs). Here, we systematically assess genomic and network-level determinants of TF evolutionary rate in yeast, and how they compare to those of generic proteins, while carefully controlling for differences of the TF protein set, such as expression level. We found significantly distinct trends relating TF evolutionary rate to mRNA expression level, codon adaptation index, the evolutionary rate of physical interaction partners, and, confirming previous reports, to protein-protein interaction degree and regulatory in-degree. We discovered that for TFs, the dominant determinants of evolutionary rate lie in the structure of the regulatory network, such as the median evolutionary rate of target genes and the fraction of species-specific target genes. Decomposing the regulatory network by edge sign, we found that this modular evolution of TFs and their targets is limited to activating regulatory relationships. We show that fast evolving TFs tend to regulate other TFs and niche-specific processes and that their targets show larger evolutionary expression changes than targets of other TFs. We also show that the positive trend relating TF regulatory in-degree and evolutionary rate is likely related to the species-specificity of the transcriptional regulation modules. Finally, we discuss likely causes for TFs' different evolutionary relationship to the physical interaction network, such as the prevalence of transient interactions in the TF subnetwork. This work suggests that positive and negative regulatory networks follow very different evolutionary rules, and that transcription factor evolution is best understood at a network- or systems-level.Jasmin Coulombe-HuntingtonYu XiaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 10, p e1002734 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Jasmin Coulombe-Huntington Yu Xia Regulatory network structure as a dominant determinant of transcription factor evolutionary rate.
description	The evolution of transcriptional regulatory networks has thus far mostly been studied at the level of cis-regulatory elements. To gain a complete understanding of regulatory network evolution we must also study the evolutionary role of trans-factors, such as transcription factors (TFs). Here, we systematically assess genomic and network-level determinants of TF evolutionary rate in yeast, and how they compare to those of generic proteins, while carefully controlling for differences of the TF protein set, such as expression level. We found significantly distinct trends relating TF evolutionary rate to mRNA expression level, codon adaptation index, the evolutionary rate of physical interaction partners, and, confirming previous reports, to protein-protein interaction degree and regulatory in-degree. We discovered that for TFs, the dominant determinants of evolutionary rate lie in the structure of the regulatory network, such as the median evolutionary rate of target genes and the fraction of species-specific target genes. Decomposing the regulatory network by edge sign, we found that this modular evolution of TFs and their targets is limited to activating regulatory relationships. We show that fast evolving TFs tend to regulate other TFs and niche-specific processes and that their targets show larger evolutionary expression changes than targets of other TFs. We also show that the positive trend relating TF regulatory in-degree and evolutionary rate is likely related to the species-specificity of the transcriptional regulation modules. Finally, we discuss likely causes for TFs' different evolutionary relationship to the physical interaction network, such as the prevalence of transient interactions in the TF subnetwork. This work suggests that positive and negative regulatory networks follow very different evolutionary rules, and that transcription factor evolution is best understood at a network- or systems-level.
format	article
author	Jasmin Coulombe-Huntington Yu Xia
author_facet	Jasmin Coulombe-Huntington Yu Xia
author_sort	Jasmin Coulombe-Huntington
title	Regulatory network structure as a dominant determinant of transcription factor evolutionary rate.
title_short	Regulatory network structure as a dominant determinant of transcription factor evolutionary rate.
title_full	Regulatory network structure as a dominant determinant of transcription factor evolutionary rate.
title_fullStr	Regulatory network structure as a dominant determinant of transcription factor evolutionary rate.
title_full_unstemmed	Regulatory network structure as a dominant determinant of transcription factor evolutionary rate.
title_sort	regulatory network structure as a dominant determinant of transcription factor evolutionary rate.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/acbd43732153438692f9ec6ef91de5a1
work_keys_str_mv	AT jasmincoulombehuntington regulatorynetworkstructureasadominantdeterminantoftranscriptionfactorevolutionaryrate AT yuxia regulatorynetworkstructureasadominantdeterminantoftranscriptionfactorevolutionaryrate
_version_	1718424748282609664

Regulatory network structure as a dominant determinant of transcription factor evolutionary rate.

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