Patterns of recombination in HIV-1M are influenced by selection disfavouring the survival of recombinants with disrupted genomic RNA and protein structures
dc.contributor.author | Golden, Michael | en_ZA |
dc.contributor.author | Muhire, Brejnev M | en_ZA |
dc.contributor.author | Semegni, Yves | en_ZA |
dc.contributor.author | Martin, Darren P | en_ZA |
dc.date.accessioned | 2016-01-11T06:53:38Z | |
dc.date.available | 2016-01-11T06:53:38Z | |
dc.date.issued | 2014 | en_ZA |
dc.description.abstract | 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. | en_ZA |
dc.identifier.apacitation | Golden, 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/11427/16287 | en_ZA |
dc.identifier.chicagocitation | Golden, 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/11427/16287 | en_ZA |
dc.identifier.citation | olden, 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.0100400 | en_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.uri | http://hdl.handle.net/11427/16287 | |
dc.identifier.uri | http://dx.doi.org/10.1371/journal.pone.0100400 | |
dc.identifier.vancouvercitation | Golden 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.iso | eng | en_ZA |
dc.publisher | Public Library of Science | en_ZA |
dc.publisher.department | Institute of Infectious Disease and Molecular Medicine | en_ZA |
dc.publisher.faculty | Faculty of Health Sciences | en_ZA |
dc.publisher.institution | University of Cape Town | |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons A | en_ZA |
dc.rights.holder | © 2014 Golden et al | en_ZA |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0 | en_ZA |
dc.source | PLoS One | en_ZA |
dc.source.uri | http://journals.plos.org/plosone | en_ZA |
dc.subject.other | Recombinant proteins | en_ZA |
dc.subject.other | Structural genomics | en_ZA |
dc.subject.other | RNA folding | en_ZA |
dc.subject.other | HIV | en_ZA |
dc.subject.other | Protein folding | en_ZA |
dc.subject.other | DNA recombination | en_ZA |
dc.subject.other | Protein structure | en_ZA |
dc.subject.other | RNA structure | en_ZA |
dc.title | Patterns of recombination in HIV-1M are influenced by selection disfavouring the survival of recombinants with disrupted genomic RNA and protein structures | en_ZA |
dc.type | Journal Article | en_ZA |
uct.type.filetype | Text | |
uct.type.filetype | Image | |
uct.type.publication | Research | en_ZA |
uct.type.resource | Article | en_ZA |
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