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Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages

2016-02-29Artigo científico Acesso aberto
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dc.contributor.authorPhelan, Jody E.
dc.contributor.authorColl, Francesc
dc.contributor.authorBergval, Indra
dc.contributor.authorAnthony, Richard M.
dc.contributor.authorWarren, Rob
dc.contributor.authorSampson, Samantha L.
dc.contributor.authorGey van Pittius, Nicolaas C.
dc.contributor.authorGlynn, Judith R.
dc.contributor.authorCrampin, Amelia C.
dc.contributor.authorAlves, Adriana
dc.contributor.authorBessa, Theolis Barbosa
dc.contributor.authorCampino, Susana
dc.contributor.authorDheda, Keertan
dc.contributor.authorGrandjean, Louis
dc.contributor.authorHasan, Rumina
dc.contributor.authorHasan, Zahra
dc.contributor.authorMiranda, Anabela
dc.contributor.authorMoore, David
dc.contributor.authorPanaiotov, Stefan
dc.contributor.authorPerdigao, Joao
dc.contributor.authorPortugal, Isabel
dc.contributor.authorSheen, Patricia
dc.contributor.authorde Oliveira Sousa, Erivelton
dc.contributor.authorStreicher, Elizabeth M.
dc.contributor.authorvan Helden, Paul D.
dc.contributor.authorViveiros, Miguel
dc.contributor.authorHibberd, Martin L.
dc.contributor.authorPain, Arnab
dc.contributor.authorMcNerney, Ruth
dc.contributor.authorClark, Taane G.
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.institutionTB, HIV and opportunistic diseases and pathogens (THOP)
dc.contributor.pblBioMed Central (BMC)
dc.date.accessioned2018-05-11T22:04:33Z
dc.date.available2018-05-11T22:04:33Z
dc.date.issued2016-02-29
dc.description.abstractBackground: Approximately 10 % of the Mycobacterium tuberculosis genome is made up of two families of genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE and PPE families are typified by their highly conserved N-terminal domains that incorporate proline-glutamate (PE) and proline-proline-glutamate (PPE) signature motifs. They are hypothesised to be important virulence factors involved with host-pathogen interactions, but their high genetic variability and complexity of analysis means they are typically disregarded in genome studies. Results: To elucidate the structure of these genes, 518 genomes from a diverse international collection of clinical isolates were de novo assembled. A further 21 reference M. tuberculosis complex genomes and long read sequence data were used to validate the approach. SNP analysis revealed that variation in the majority of the 168 pe/ppe genes studied was consistent with lineage. Several recombination hotspots were identified, notably pe_pgrs3 and pe_pgrs17. Evidence of positive selection was revealed in 65 pe/ppe genes, including epitopes potentially binding to major histocompatibility complex molecules. Conclusions: This, the first comprehensive study of the pe and ppe genes, provides important insight into M. tuberculosis diversity and has significant implications for vaccine development.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent1687531
dc.identifier.doi10.1186/s12864-016-2467-y
dc.identifier.otherPURE: 2316883
dc.identifier.otherPURE UUID: 78d88a52-46c5-4091-b067-402893fa9fb5
dc.identifier.otherScopus: 84959198490
dc.identifier.otherPubMed: 26923687
dc.identifier.otherPubMedCentral: 4770551
dc.identifier.otherWOS: 000371594300002
dc.identifier.otherORCID: /0000-0001-9676-6251/work/45270507
dc.identifier.urihttp://www.scopus.com/inward/record.url?scp=84959198490&partnerID=8YFLogxK
dc.identifier.urlhttps://www.scopus.com/pages/publications/84959198490
dc.language.isoeng
dc.peerreviewedyes
dc.subjectPOSITIVE SELECTION
dc.subjectLARGE GENOMES
dc.subjectPROTEIN
dc.subjectSTRAINS
dc.subjectEVOLUTION
dc.subjectSEQUENCE
dc.subjectINSIGHTS
dc.subjectASSEMBLIES
dc.subjectDIVERSITY
dc.subjectVIRULENCE
dc.subjectBiotechnology
dc.subjectGenetics
dc.subjectInfectious Diseases
dc.subjectDrug Discovery
dc.subjectSDG 3 - Good Health and Well-being
dc.titleRecombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineagesen
dc.typejournal article
degois.publication.issue1
degois.publication.titleBMC Genomics
degois.publication.volume17
dspace.entity.typePublication
rcaap.rightsopenAccess

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