Comparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and apparent absence of selective constraints

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dc.contributor.authorMcEvoy, Christopher R. E.en_ZA
dc.contributor.authorCloete, Rubenen_ZA
dc.contributor.authorMuller, Bornaen_ZA
dc.contributor.authorSchurch, Anita C.en_ZA
dc.contributor.authorVan Helden, Paul D.en_ZA
dc.contributor.authorGagneux, Sebastienen_ZA
dc.contributor.authorWarren, Robin M.en_ZA
dc.contributor.authorGey van Pittius, Nicolaas C.en_ZA
dc.date.accessioned2013-07-03T08:19:11Z
dc.date.available2013-07-03T08:19:11Z
dc.date.issued2012-04-04
dc.descriptionCITATION: McEvoy, C. R. E. et al. 2012. Comparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and apparent absence of selective constraints. PLoS ONE, 7(4): e30593, doi:10.1371/journal.pone.0030593.
dc.descriptionThe original publication is available at http://journals.plos.org/plosone
dc.description.abstractMycobacterium tuberculosis complex (MTBC) genomes contain 2 large gene families termed pe and ppe. The function of pe/ppe proteins remains enigmatic but studies suggest that they are secreted or cell surface associated and are involved in bacterial virulence. Previous studies have also shown that some pe/ppe genes are polymorphic, a finding that suggests involvement in antigenic variation. Using comparative sequence analysis of 18 publicly available MTBC whole genome sequences, we have performed alignments of 33 pe (excluding pe_pgrs) and 66 ppe genes in order to detect the frequency and nature of genetic variation. This work has been supplemented by whole gene sequencing of 14 pe/ppe (including 5 pe_pgrs) genes in a cohort of 40 diverse and well defined clinical isolates covering all the main lineages of the M. tuberculosis phylogenetic tree. We show that nsSNP's in pe (excluding pgrs) and ppe genes are 3.0 and 3.3 times higher than in non-pe/ppe genes respectively and that numerous other mutation types are also present at a high frequency. It has previously been shown that non-pe/ppe M. tuberculosis genes display a remarkably low level of purifying selection. Here, we also show that compared to these genes those of the pe/ppe families show a further reduction of selection pressure that suggests neutral evolution. This is inconsistent with the positive selection pressure of “classical” antigenic variation. Finally, by analyzing such a large number of genes we were able to detect large differences in mutation type and frequency between both individual genes and gene sub-families. The high variation rates and absence of selective constraints provides valuable insights into potential pe/ppe function. Since pe/ppe proteins are highly antigenic and have been studied as potential vaccine components these results should also prove informative for aspects of M. tuberculosis vaccine design.
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030593
dc.description.versionPublisher's version
dc.format.extent12 pages
dc.identifier.citationMcEvoy, C. R. E. et al. 2012. Comparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and apparent absence of selective constraints. PLoS ONE, 7(4): e30593, doi:10.1371/journal.pone.0030593.
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0030593
dc.identifier.urihttp://hdl.handle.net/10019.1/81872
dc.language.isoen
dc.publisherPublic Library of Science
dc.rights.holderAuthors retain copyright
dc.subjectTuberculosisen_ZA
dc.subjectTuberculosis -- Genetic aspectsen_ZA
dc.titleComparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and apparent absence of selective constraintsen_ZA
dc.typeArticle
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