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Phylogenomic Identification of Regulatory Sequences in Bacteria: an Analysis of Statistical Power and an Application to Borrelia burgdorferi Sensu Lato
Phylogenomic footprinting is an approach for ab initio identification of genome-wide regulatory elements in bacterial species based on sequence conservation. The statistical power of the phylogenomic approach depends on the degree of sequence conservation, the length of regulatory elements, and the...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453575/ https://www.ncbi.nlm.nih.gov/pubmed/25873371 http://dx.doi.org/10.1128/mBio.00011-15 |
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author | Martin, Che I. Sukarna, Tika Y. Akther, Saymon Ramrattan, Girish Pagan, Pedro Di, Lia Mongodin, Emmanuel F. Fraser, Claire M. Schutzer, Steven E. Luft, Benjamin J. Casjens, Sherwood R. Qiu, Wei-Gang |
author_facet | Martin, Che I. Sukarna, Tika Y. Akther, Saymon Ramrattan, Girish Pagan, Pedro Di, Lia Mongodin, Emmanuel F. Fraser, Claire M. Schutzer, Steven E. Luft, Benjamin J. Casjens, Sherwood R. Qiu, Wei-Gang |
author_sort | Martin, Che I. |
collection | PubMed |
description | Phylogenomic footprinting is an approach for ab initio identification of genome-wide regulatory elements in bacterial species based on sequence conservation. The statistical power of the phylogenomic approach depends on the degree of sequence conservation, the length of regulatory elements, and the level of phylogenetic divergence among genomes. Building on an earlier model, we propose a binomial model that uses synonymous tree lengths as neutral expectations for determining the statistical significance of conserved intergenic spacer (IGS) sequences. Simulations show that the binomial model is robust to variations in the value of evolutionary parameters, including base frequencies and the transition-to-transversion ratio. We used the model to search for regulatory sequences in the Lyme disease species group (Borrelia burgdorferi sensu lato) using 23 genomes. The model indicates that the currently available set of Borrelia genomes would not yield regulatory sequences shorter than five bases, suggesting that genome sequences of additional B. burgdorferi sensu lato species are needed. Nevertheless, we show that previously known regulatory elements are indeed strongly conserved in sequence or structure across these Borrelia species. Further, we predict with sufficient confidence two new RpoS binding sites, 39 promoters, 19 transcription terminators, 28 noncoding RNAs, and four sets of coregulated genes. These putative cis- and trans-regulatory elements suggest novel, Borrelia-specific mechanisms regulating the transition between the tick and host environments, a key adaptation and virulence mechanism of B. burgdorferi. Alignments of IGS sequences are available on BorreliaBase.org, an online database of orthologous open reading frame (ORF) and IGS sequences in Borrelia. |
format | Online Article Text |
id | pubmed-4453575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-44535752015-06-03 Phylogenomic Identification of Regulatory Sequences in Bacteria: an Analysis of Statistical Power and an Application to Borrelia burgdorferi Sensu Lato Martin, Che I. Sukarna, Tika Y. Akther, Saymon Ramrattan, Girish Pagan, Pedro Di, Lia Mongodin, Emmanuel F. Fraser, Claire M. Schutzer, Steven E. Luft, Benjamin J. Casjens, Sherwood R. Qiu, Wei-Gang mBio Research Article Phylogenomic footprinting is an approach for ab initio identification of genome-wide regulatory elements in bacterial species based on sequence conservation. The statistical power of the phylogenomic approach depends on the degree of sequence conservation, the length of regulatory elements, and the level of phylogenetic divergence among genomes. Building on an earlier model, we propose a binomial model that uses synonymous tree lengths as neutral expectations for determining the statistical significance of conserved intergenic spacer (IGS) sequences. Simulations show that the binomial model is robust to variations in the value of evolutionary parameters, including base frequencies and the transition-to-transversion ratio. We used the model to search for regulatory sequences in the Lyme disease species group (Borrelia burgdorferi sensu lato) using 23 genomes. The model indicates that the currently available set of Borrelia genomes would not yield regulatory sequences shorter than five bases, suggesting that genome sequences of additional B. burgdorferi sensu lato species are needed. Nevertheless, we show that previously known regulatory elements are indeed strongly conserved in sequence or structure across these Borrelia species. Further, we predict with sufficient confidence two new RpoS binding sites, 39 promoters, 19 transcription terminators, 28 noncoding RNAs, and four sets of coregulated genes. These putative cis- and trans-regulatory elements suggest novel, Borrelia-specific mechanisms regulating the transition between the tick and host environments, a key adaptation and virulence mechanism of B. burgdorferi. Alignments of IGS sequences are available on BorreliaBase.org, an online database of orthologous open reading frame (ORF) and IGS sequences in Borrelia. American Society of Microbiology 2015-04-14 /pmc/articles/PMC4453575/ /pubmed/25873371 http://dx.doi.org/10.1128/mBio.00011-15 Text en Copyright © 2015 Martin et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Martin, Che I. Sukarna, Tika Y. Akther, Saymon Ramrattan, Girish Pagan, Pedro Di, Lia Mongodin, Emmanuel F. Fraser, Claire M. Schutzer, Steven E. Luft, Benjamin J. Casjens, Sherwood R. Qiu, Wei-Gang Phylogenomic Identification of Regulatory Sequences in Bacteria: an Analysis of Statistical Power and an Application to Borrelia burgdorferi Sensu Lato |
title | Phylogenomic Identification of Regulatory Sequences in Bacteria: an Analysis of Statistical Power and an Application to Borrelia burgdorferi Sensu Lato |
title_full | Phylogenomic Identification of Regulatory Sequences in Bacteria: an Analysis of Statistical Power and an Application to Borrelia burgdorferi Sensu Lato |
title_fullStr | Phylogenomic Identification of Regulatory Sequences in Bacteria: an Analysis of Statistical Power and an Application to Borrelia burgdorferi Sensu Lato |
title_full_unstemmed | Phylogenomic Identification of Regulatory Sequences in Bacteria: an Analysis of Statistical Power and an Application to Borrelia burgdorferi Sensu Lato |
title_short | Phylogenomic Identification of Regulatory Sequences in Bacteria: an Analysis of Statistical Power and an Application to Borrelia burgdorferi Sensu Lato |
title_sort | phylogenomic identification of regulatory sequences in bacteria: an analysis of statistical power and an application to borrelia burgdorferi sensu lato |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453575/ https://www.ncbi.nlm.nih.gov/pubmed/25873371 http://dx.doi.org/10.1128/mBio.00011-15 |
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