Extensive purifying selection acting on synonymous sites in HIV-1 Group M sequences

dc.contributor.authorNgandu, Nobubeloen_ZA
dc.contributor.authorScheffler, Konraden_ZA
dc.contributor.authorMoore, Pennyen_ZA
dc.contributor.authorWoodman, Zendaen_ZA
dc.contributor.authorMartin, Darrenen_ZA
dc.contributor.authorSeoighe, Cathalen_ZA
dc.date.accessioned2015-10-28T07:01:12Z
dc.date.available2015-10-28T07:01:12Z
dc.date.issued2008en_ZA
dc.description.abstractBACKGROUND: Positive selection pressure acting on protein-coding sequences is usually inferred when the rate of nonsynonymous substitution is greater than the synonymous rate. However, purifying selection acting directly on the nucleotide sequence can lower the synonymous substitution rate. This could result in false inference of positive selection because when synonymous changes at some sites are under purifying selection, the average synonymous rate is an underestimate of the neutral rate of evolution. Even though HIV-1 coding sequences contain a number of regions that function at the nucleotide level, and are thus likely to be affected by purifying selection, studies of positive selection assume that synonymous substitutions can be used to estimate the neutral rate of evolution. RESULTS: We modelled site-to-site variation in the synonymous substitution rate across coding regions of the HIV-1 genome. Synonymous substitution rates were found to vary significantly within and between genes. Surprisingly, regions of the genome that encode proteins in more than one frame had significantly higher synonymous substitution rates than regions coding in a single frame. We found evidence of strong purifying selection pressure affecting synonymous mutations in fourteen regions with known functions. These included an exonic splicing enhancer, the rev-responsive element, the poly-purine tract and a transcription factor binding site. A further five highly conserved regions were located within known functional domains. We also found four conserved regions located in env and vpu which have not been characterized previously. CONCLUSION: We provide the coordinates of genomic regions with markedly lower synonymous substitution rates, which are putatively under the influence of strong purifying selection pressure at the nucleotide level as well as regions encoding proteins in more than one frame. These regions should be excluded from studies of positive selection acting on HIV-1 coding regions.en_ZA
dc.identifier.apacitationNgandu, N., Scheffler, K., Moore, P., Woodman, Z., Martin, D., & Seoighe, C. (2008). Extensive purifying selection acting on synonymous sites in HIV-1 Group M sequences. <i>Virology Journal</i>, http://hdl.handle.net/11427/14450en_ZA
dc.identifier.chicagocitationNgandu, Nobubelo, Konrad Scheffler, Penny Moore, Zenda Woodman, Darren Martin, and Cathal Seoighe "Extensive purifying selection acting on synonymous sites in HIV-1 Group M sequences." <i>Virology Journal</i> (2008) http://hdl.handle.net/11427/14450en_ZA
dc.identifier.citationNgandu, N. K., Scheffler, K., Moore, P., Woodman, Z., Martin, D., & Seoighe, C. (2008). Extensive purifying selection acting on synonymous sites in HIV-1 Group M sequences. Virol. J, 5(1), 160.en_ZA
dc.identifier.ris TY - Journal Article AU - Ngandu, Nobubelo AU - Scheffler, Konrad AU - Moore, Penny AU - Woodman, Zenda AU - Martin, Darren AU - Seoighe, Cathal AB - BACKGROUND: Positive selection pressure acting on protein-coding sequences is usually inferred when the rate of nonsynonymous substitution is greater than the synonymous rate. However, purifying selection acting directly on the nucleotide sequence can lower the synonymous substitution rate. This could result in false inference of positive selection because when synonymous changes at some sites are under purifying selection, the average synonymous rate is an underestimate of the neutral rate of evolution. Even though HIV-1 coding sequences contain a number of regions that function at the nucleotide level, and are thus likely to be affected by purifying selection, studies of positive selection assume that synonymous substitutions can be used to estimate the neutral rate of evolution. RESULTS: We modelled site-to-site variation in the synonymous substitution rate across coding regions of the HIV-1 genome. Synonymous substitution rates were found to vary significantly within and between genes. Surprisingly, regions of the genome that encode proteins in more than one frame had significantly higher synonymous substitution rates than regions coding in a single frame. We found evidence of strong purifying selection pressure affecting synonymous mutations in fourteen regions with known functions. These included an exonic splicing enhancer, the rev-responsive element, the poly-purine tract and a transcription factor binding site. A further five highly conserved regions were located within known functional domains. We also found four conserved regions located in env and vpu which have not been characterized previously. CONCLUSION: We provide the coordinates of genomic regions with markedly lower synonymous substitution rates, which are putatively under the influence of strong purifying selection pressure at the nucleotide level as well as regions encoding proteins in more than one frame. These regions should be excluded from studies of positive selection acting on HIV-1 coding regions. DA - 2008 DB - OpenUCT DO - 10.1186/1743-422X-5-160 DP - University of Cape Town J1 - Virology Journal LK - https://open.uct.ac.za PB - University of Cape Town PY - 2008 T1 - Extensive purifying selection acting on synonymous sites in HIV-1 Group M sequences TI - Extensive purifying selection acting on synonymous sites in HIV-1 Group M sequences UR - http://hdl.handle.net/11427/14450 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14450
dc.identifier.urihttp://dx.doi.org/10.1186/1743-422X-5-160
dc.identifier.vancouvercitationNgandu N, Scheffler K, Moore P, Woodman Z, Martin D, Seoighe C. Extensive purifying selection acting on synonymous sites in HIV-1 Group M sequences. Virology Journal. 2008; http://hdl.handle.net/11427/14450.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2008 Ngandu et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceVirology Journalen_ZA
dc.source.urihttp://www.virologyj.com/en_ZA
dc.subject.otherAmino Acid Substitutionen_ZA
dc.subject.otherBase Sequenceen_ZA
dc.subject.otherGenetic Variationen_ZA
dc.subject.otherHIV-1en_ZA
dc.subject.otherSelection, Geneticen_ZA
dc.titleExtensive purifying selection acting on synonymous sites in HIV-1 Group M sequencesen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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