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Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes

BACKGROUND: It is known that mRNA folding can affect and regulate various gene expression steps both in living organisms and in viruses. Previous studies have recognized functional RNA structures in the genome of the Dengue virus. However, these studies usually focused either on the viral untranslat...

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Autores principales: Goz, Eli, Tuller, Tamir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602183/
https://www.ncbi.nlm.nih.gov/pubmed/26449467
http://dx.doi.org/10.1186/1471-2164-16-S10-S4
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author Goz, Eli
Tuller, Tamir
author_facet Goz, Eli
Tuller, Tamir
author_sort Goz, Eli
collection PubMed
description BACKGROUND: It is known that mRNA folding can affect and regulate various gene expression steps both in living organisms and in viruses. Previous studies have recognized functional RNA structures in the genome of the Dengue virus. However, these studies usually focused either on the viral untranslated regions or on very specific and limited regions at the beginning of the coding sequences, in a limited number of strains, and without considering evolutionary selection. RESULTS: Here we performed the first large scale comprehensive genomics analysis of selection for local mRNA folding strength in the Dengue virus coding sequences, based on a total of 1,670 genomes and 4 serotypes. Our analysis identified clusters of positions along the coding regions that may undergo a conserved evolutionary selection for strong or weak local folding maintained across different viral variants. Specifically, 53-66 clusters for strong folding and 49-73 clusters for weak folding (depending on serotype) aggregated of positions with a significant conservation of folding energy signals (related to partially overlapping local genomic regions) were recognized. In addition, up to 7% of these positions were found to be conserved in more than 90% of the viral genomes. Although some of the identified positions undergo frequent synonymous / non-synonymous substitutions, the selection for folding strength therein is preserved, and thus cannot be trivially explained based on sequence conservation alone. CONCLUSIONS: The fact that many of the positions with significant folding related signals are conserved among different Dengue variants suggests that a better understanding of the mRNA structures in the corresponding regions may promote the development of prospective anti- Dengue vaccination strategies. The comparative genomics approach described here can be employed in the future for detecting functional regions in other pathogens with very high mutations rates.
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spelling pubmed-46021832015-10-13 Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes Goz, Eli Tuller, Tamir BMC Genomics Research BACKGROUND: It is known that mRNA folding can affect and regulate various gene expression steps both in living organisms and in viruses. Previous studies have recognized functional RNA structures in the genome of the Dengue virus. However, these studies usually focused either on the viral untranslated regions or on very specific and limited regions at the beginning of the coding sequences, in a limited number of strains, and without considering evolutionary selection. RESULTS: Here we performed the first large scale comprehensive genomics analysis of selection for local mRNA folding strength in the Dengue virus coding sequences, based on a total of 1,670 genomes and 4 serotypes. Our analysis identified clusters of positions along the coding regions that may undergo a conserved evolutionary selection for strong or weak local folding maintained across different viral variants. Specifically, 53-66 clusters for strong folding and 49-73 clusters for weak folding (depending on serotype) aggregated of positions with a significant conservation of folding energy signals (related to partially overlapping local genomic regions) were recognized. In addition, up to 7% of these positions were found to be conserved in more than 90% of the viral genomes. Although some of the identified positions undergo frequent synonymous / non-synonymous substitutions, the selection for folding strength therein is preserved, and thus cannot be trivially explained based on sequence conservation alone. CONCLUSIONS: The fact that many of the positions with significant folding related signals are conserved among different Dengue variants suggests that a better understanding of the mRNA structures in the corresponding regions may promote the development of prospective anti- Dengue vaccination strategies. The comparative genomics approach described here can be employed in the future for detecting functional regions in other pathogens with very high mutations rates. BioMed Central 2015-10-02 /pmc/articles/PMC4602183/ /pubmed/26449467 http://dx.doi.org/10.1186/1471-2164-16-S10-S4 Text en Copyright © 2015 Goz and Tuller http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Goz, Eli
Tuller, Tamir
Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes
title Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes
title_full Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes
title_fullStr Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes
title_full_unstemmed Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes
title_short Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes
title_sort widespread signatures of local mrna folding structure selection in four dengue virus serotypes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602183/
https://www.ncbi.nlm.nih.gov/pubmed/26449467
http://dx.doi.org/10.1186/1471-2164-16-S10-S4
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