Phelan, Jody E;
Coll, Francesc;
Bergval, Indra;
Anthony, Richard M;
Warren, Rob;
Sampson, Samantha L;
van Pittius, Nicolaas C Gey;
... Clark, Taane G; + view all
(2016)
Recombination in pe/ppe genes contributes
to genetic variation in Mycobacterium
tuberculosis lineages.
BMC GENOMICS
, 17
, Article 151. 10.1186/s12864-016-2467-y.
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Abstract
Background: 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.
| Type: | Article |
|---|---|
| Title: | Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s12864-016-2467-y |
| Publisher version: | https://doi.org/10.1186/s12864-016-2467-y |
| Language: | English |
| Additional information: | © The Author(s), 2016. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Tuberculosis, Major Histocompatibility Complex Molecule, Mycobacterium Tuberculosis Complex, Tuberculosis Lineage, Variable Selective Pressure |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10176767 |
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