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Functional characterization of motif sequences under purifying selection
Diverse life forms are driven by the evolution of gene regulatory programs including changes in regulator proteins and cis-regulatory elements. Alterations of cis-regulatory elements are likely to dominate the evolution of the gene regulatory networks, as they are subjected to smaller selective cons...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575792/ https://www.ncbi.nlm.nih.gov/pubmed/23303791 http://dx.doi.org/10.1093/nar/gks1456 |
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author | Chen, De-Hua Chang, Andrew Ying-Fei Liao, Ben-Yang Yeang, Chen-Hsiang |
author_facet | Chen, De-Hua Chang, Andrew Ying-Fei Liao, Ben-Yang Yeang, Chen-Hsiang |
author_sort | Chen, De-Hua |
collection | PubMed |
description | Diverse life forms are driven by the evolution of gene regulatory programs including changes in regulator proteins and cis-regulatory elements. Alterations of cis-regulatory elements are likely to dominate the evolution of the gene regulatory networks, as they are subjected to smaller selective constraints compared with proteins and hence may evolve quickly to adapt the environment. Prior studies on cis-regulatory element evolution focus primarily on sequence substitutions of known transcription factor-binding motifs. However, evolutionary models for the dynamics of motif occurrence are relatively rare, and comprehensive characterization of the evolution of all possible motif sequences has not been pursued. In the present study, we propose an algorithm to estimate the strength of purifying selection of a motif sequence based on an evolutionary model capturing the birth and death of motif occurrences on promoters. We term this measure as the ‘evolutionary retention coefficient’, as it is related yet distinct from the canonical definition of selection coefficient in population genetics. Using this algorithm, we estimate and report the evolutionary retention coefficients of all possible 10-nucleotide sequences from the aligned promoter sequences of 27 748. orthologous gene families in 34 mammalian species. Intriguingly, the evolutionary retention coefficients of motifs are intimately associated with their functional relevance. Top-ranking motifs (sorted by evolutionary retention coefficients) are significantly enriched with transcription factor-binding sequences according to the curated knowledge from the TRANSFAC database and the ChIP-seq data generated from the ENCODE Consortium. Moreover, genes harbouring high-scoring motifs on their promoters retain significantly coherent expression profiles, and those genes are over-represented in the functional classes involved in gene regulation. The validation results reveal the dependencies between natural selection and functions of cis-regulatory elements and shed light on the evolution of gene regulatory networks. |
format | Online Article Text |
id | pubmed-3575792 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35757922013-02-19 Functional characterization of motif sequences under purifying selection Chen, De-Hua Chang, Andrew Ying-Fei Liao, Ben-Yang Yeang, Chen-Hsiang Nucleic Acids Res Computational Biology Diverse life forms are driven by the evolution of gene regulatory programs including changes in regulator proteins and cis-regulatory elements. Alterations of cis-regulatory elements are likely to dominate the evolution of the gene regulatory networks, as they are subjected to smaller selective constraints compared with proteins and hence may evolve quickly to adapt the environment. Prior studies on cis-regulatory element evolution focus primarily on sequence substitutions of known transcription factor-binding motifs. However, evolutionary models for the dynamics of motif occurrence are relatively rare, and comprehensive characterization of the evolution of all possible motif sequences has not been pursued. In the present study, we propose an algorithm to estimate the strength of purifying selection of a motif sequence based on an evolutionary model capturing the birth and death of motif occurrences on promoters. We term this measure as the ‘evolutionary retention coefficient’, as it is related yet distinct from the canonical definition of selection coefficient in population genetics. Using this algorithm, we estimate and report the evolutionary retention coefficients of all possible 10-nucleotide sequences from the aligned promoter sequences of 27 748. orthologous gene families in 34 mammalian species. Intriguingly, the evolutionary retention coefficients of motifs are intimately associated with their functional relevance. Top-ranking motifs (sorted by evolutionary retention coefficients) are significantly enriched with transcription factor-binding sequences according to the curated knowledge from the TRANSFAC database and the ChIP-seq data generated from the ENCODE Consortium. Moreover, genes harbouring high-scoring motifs on their promoters retain significantly coherent expression profiles, and those genes are over-represented in the functional classes involved in gene regulation. The validation results reveal the dependencies between natural selection and functions of cis-regulatory elements and shed light on the evolution of gene regulatory networks. Oxford University Press 2013-02 2013-01-08 /pmc/articles/PMC3575792/ /pubmed/23303791 http://dx.doi.org/10.1093/nar/gks1456 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Computational Biology Chen, De-Hua Chang, Andrew Ying-Fei Liao, Ben-Yang Yeang, Chen-Hsiang Functional characterization of motif sequences under purifying selection |
title | Functional characterization of motif sequences under purifying selection |
title_full | Functional characterization of motif sequences under purifying selection |
title_fullStr | Functional characterization of motif sequences under purifying selection |
title_full_unstemmed | Functional characterization of motif sequences under purifying selection |
title_short | Functional characterization of motif sequences under purifying selection |
title_sort | functional characterization of motif sequences under purifying selection |
topic | Computational Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575792/ https://www.ncbi.nlm.nih.gov/pubmed/23303791 http://dx.doi.org/10.1093/nar/gks1456 |
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