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      Whole Genome Sequence and Phylogenetic Analysis Show Helicobacter pylori Strains from Latin America Have Followed a Unique Evolution Pathway

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          Abstract

          Helicobacter pylori (HP) genetics may determine its clinical outcomes. Despite high prevalence of HP infection in Latin America (LA), there have been no phylogenetic studies in the region. We aimed to understand the structure of HP populations in LA mestizo individuals, where gastric cancer incidence remains high. The genome of 107 HP strains from Mexico, Nicaragua and Colombia were analyzed with 59 publicly available worldwide genomes. To study bacterial relationship on whole genome level we propose a virtual hybridization technique using thousands of high-entropy 13 bp DNA probes to generate fingerprints. Phylogenetic virtual genome fingerprint (VGF) was compared with Multi Locus Sequence Analysis (MLST) and with phylogenetic analyses of cagPAI virulence island sequences. With MLST some Nicaraguan and Mexican strains clustered close to Africa isolates, whereas European isolates were spread without clustering and intermingled with LA isolates. VGF analysis resulted in increased resolution of populations, separating European from LA strains. Furthermore, clusters with exclusively Colombian, Mexican, or Nicaraguan strains were observed, where the Colombian cluster separated from Europe, Asia, and Africa, while Nicaraguan and Mexican clades grouped close to Africa. In addition, a mixed large LA cluster including Mexican, Colombian, Nicaraguan, Peruvian, and Salvadorian strains was observed; all LA clusters separated from the Amerind clade. With cagPAI sequence analyses LA clades clearly separated from Europe, Asia and Amerind, and Colombian strains formed a single cluster. A NeighborNet analyses suggested frequent and recent recombination events particularly among LA strains. Results suggests that in the new world, H. pylori has evolved to fit mestizo LA populations, already 500 years after the Spanish colonization. This co-adaption may account for regional variability in gastric cancer risk.

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          Most cited references35

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          nhmmer: DNA homology search with profile HMMs

          Summary: Sequence database searches are an essential part of molecular biology, providing information about the function and evolutionary history of proteins, RNA molecules and DNA sequence elements. We present a tool for DNA/DNA sequence comparison that is built on the HMMER framework, which applies probabilistic inference methods based on hidden Markov models to the problem of homology search. This tool, called nhmmer, enables improved detection of remote DNA homologs, and has been used in combination with Dfam and RepeatMasker to improve annotation of transposable elements in the human genome. Availability: nhmmer is a part of the new HMMER3.1 release. Source code and documentation can be downloaded from http://hmmer.org. HMMER3.1 is freely licensed under the GNU GPLv3 and should be portable to any POSIX-compliant operating system, including Linux and Mac OS/X. Contact: wheelert@janelia.hhmi.org
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            Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994.

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              RevTrans: Multiple alignment of coding DNA from aligned amino acid sequences.

              The simple fact that proteins are built from 20 amino acids while DNA only contains four different bases, means that the 'signal-to-noise ratio' in protein sequence alignments is much better than in alignments of DNA. Besides this information-theoretical advantage, protein alignments also benefit from the information that is implicit in empirical substitution matrices such as BLOSUM-62. Taken together with the generally higher rate of synonymous mutations over non-synonymous ones, this means that the phylogenetic signal disappears much more rapidly from DNA sequences than from the encoded proteins. It is therefore preferable to align coding DNA at the amino acid level and it is for this purpose we have constructed the program RevTrans. RevTrans constructs a multiple DNA alignment by: (i) translating the DNA; (ii) aligning the resulting peptide sequences; and (iii) building a multiple DNA alignment by 'reverse translation' of the aligned protein sequences. In the resulting DNA alignment, gaps occur in groups of three corresponding to entire codons, and analogous codon positions are therefore always lined up. These features are useful when constructing multiple DNA alignments for phylogenetic analysis. RevTrans also accepts user-provided protein alignments for greater control of the alignment process. The RevTrans web server is freely available at http://www.cbs.dtu.dk/services/RevTrans/.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                28 February 2017
                2017
                : 7
                : 50
                Affiliations
                [1] 1Laboratorio de Biotecnología y Bioinformática Genómica, ENCB, Instituto Politécnico Nacional Ciudad de México, Mexico
                [2] 2Department of Oncology and of Pathology, Wayne State University School of Medicine Detroit, MI, USA
                [3] 3Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerologia Bogota, Colombia
                [4] 4Dipartmento di Ricerca Traslazionale e Nuove Tecnologie in Medicina e Chirurgia, Università di Pisa Pisa, Italy
                [5] 5Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet Stockholm, Sweden
                [6] 6Unidad de Investigacion en Enfermedades Infecciosas, IMSS Ciudad de México, Mexico
                [7] 7Genomic Epidemiology Group, German Cancer Research Center (DKFZ) Heidelberg, Germany
                Author notes

                Edited by: D. Scott Merrell, Uniformed Services University of the Health Sciences, USA

                Reviewed by: Karen Ottemann, University of California, Santa Cruz, USA; Francis Mégraud, Université de Bordeaux, France

                *Correspondence: Javier Torres uimeip@ 123456gmail.com
                Article
                10.3389/fcimb.2017.00050
                5328995
                28293542
                d1f78598-ae97-46be-8aed-33b73b987943
                Copyright © 2017 Muñoz-Ramírez, Mendez-Tenorio, Kato, Bravo, Rizzato, Thorell, Torres, Aviles-Jimenez, Camorlinga, Canzian and Torres.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 November 2016
                : 10 February 2017
                Page count
                Figures: 5, Tables: 1, Equations: 0, References: 49, Pages: 12, Words: 8316
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: 5R21CA182822
                Categories
                Microbiology
                Original Research

                Infectious disease & Microbiology
                h. pylori,phylogenetic analysis,whole genome sequence,latin america

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