Patterns of recombination in HIV-1M are influenced by selection disfavouring the survival of recombinants with disrupted genomic RNA and protein structures

dc.contributor.authorGolden, Michaelen_ZA
dc.contributor.authorMuhire, Brejnev Men_ZA
dc.contributor.authorSemegni, Yvesen_ZA
dc.contributor.authorMartin, Darren Pen_ZA
dc.date.accessioned2016-01-11T06:53:38Z
dc.date.available2016-01-11T06:53:38Z
dc.date.issued2014en_ZA
dc.description.abstractGenetic recombination is a major contributor to the ongoing diversification of HIV. It is clearly apparent that across the HIV-genome there are defined recombination hot and cold spots which tend to co-localise both with genomic secondary structures and with either inter-gene boundaries or intra-gene domain boundaries. There is also good evidence that most recombination breakpoints that are detectable within the genes of natural HIV recombinants are likely to be minimally disruptive of intra-protein amino acid contacts and that these breakpoints should therefore have little impact on protein folding. Here we further investigate the impact on patterns of genetic recombination in HIV of selection favouring the maintenance of functional RNA and protein structures. We confirm that chimaeric Gag p24, reverse transcriptase, integrase, gp120 and Nef proteins that are expressed by natural HIV-1 recombinants have significantly lower degrees of predicted folding disruption than randomly generated recombinants. Similarly, we use a novel single-stranded RNA folding disruption test to show that there is significant, albeit weak, evidence that natural HIV recombinants tend to have genomic secondary structures that more closely resemble parental structures than do randomly generated recombinants. These results are consistent with the hypothesis that natural selection has acted both in the short term to purge recombinants with disrupted RNA and protein folds, and in the longer term to modify the genome architecture of HIV to ensure that recombination prone sites correspond with those where recombination will be minimally deleterious.en_ZA
dc.identifier.apacitationGolden, M., Muhire, B. M., Semegni, Y., & Martin, D. P. (2014). Patterns of recombination in HIV-1M are influenced by selection disfavouring the survival of recombinants with disrupted genomic RNA and protein structures. <i>PLoS One</i>, http://hdl.handle.net/11427/16287en_ZA
dc.identifier.chicagocitationGolden, Michael, Brejnev M Muhire, Yves Semegni, and Darren P Martin "Patterns of recombination in HIV-1M are influenced by selection disfavouring the survival of recombinants with disrupted genomic RNA and protein structures." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/16287en_ZA
dc.identifier.citationolden, M., Muhire, B. M., Semegni, Y., & Martin, D. P. (2013). Patterns of recombination in HIV-1M are influenced by selection disfavouring the survival of recombinants with disrupted genomic RNA and protein structures. PloS one, 9(6), e100400. doi:10.1371/journal.pone.0100400en_ZA
dc.identifier.ris TY - Journal Article AU - Golden, Michael AU - Muhire, Brejnev M AU - Semegni, Yves AU - Martin, Darren P AB - Genetic recombination is a major contributor to the ongoing diversification of HIV. It is clearly apparent that across the HIV-genome there are defined recombination hot and cold spots which tend to co-localise both with genomic secondary structures and with either inter-gene boundaries or intra-gene domain boundaries. There is also good evidence that most recombination breakpoints that are detectable within the genes of natural HIV recombinants are likely to be minimally disruptive of intra-protein amino acid contacts and that these breakpoints should therefore have little impact on protein folding. Here we further investigate the impact on patterns of genetic recombination in HIV of selection favouring the maintenance of functional RNA and protein structures. We confirm that chimaeric Gag p24, reverse transcriptase, integrase, gp120 and Nef proteins that are expressed by natural HIV-1 recombinants have significantly lower degrees of predicted folding disruption than randomly generated recombinants. Similarly, we use a novel single-stranded RNA folding disruption test to show that there is significant, albeit weak, evidence that natural HIV recombinants tend to have genomic secondary structures that more closely resemble parental structures than do randomly generated recombinants. These results are consistent with the hypothesis that natural selection has acted both in the short term to purge recombinants with disrupted RNA and protein folds, and in the longer term to modify the genome architecture of HIV to ensure that recombination prone sites correspond with those where recombination will be minimally deleterious. DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0100400 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Patterns of recombination in HIV-1M are influenced by selection disfavouring the survival of recombinants with disrupted genomic RNA and protein structures TI - Patterns of recombination in HIV-1M are influenced by selection disfavouring the survival of recombinants with disrupted genomic RNA and protein structures UR - http://hdl.handle.net/11427/16287 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16287
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0100400
dc.identifier.vancouvercitationGolden M, Muhire BM, Semegni Y, Martin DP. Patterns of recombination in HIV-1M are influenced by selection disfavouring the survival of recombinants with disrupted genomic RNA and protein structures. PLoS One. 2014; http://hdl.handle.net/11427/16287.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_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 Aen_ZA
dc.rights.holder© 2014 Golden et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherRecombinant proteinsen_ZA
dc.subject.otherStructural genomicsen_ZA
dc.subject.otherRNA foldingen_ZA
dc.subject.otherHIVen_ZA
dc.subject.otherProtein foldingen_ZA
dc.subject.otherDNA recombinationen_ZA
dc.subject.otherProtein structureen_ZA
dc.subject.otherRNA structureen_ZA
dc.titlePatterns of recombination in HIV-1M are influenced by selection disfavouring the survival of recombinants with disrupted genomic RNA and protein structuresen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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