PMID- 21935448 OWN - NLM STAT- MEDLINE DCOM- 20120228 LR - 20211020 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 6 IP - 9 DP - 2011 TI - "Pseudo-Beijing": evidence for convergent evolution in the direct repeat region of Mycobacterium tuberculosis. PG - e24737 LID - 10.1371/journal.pone.0024737 [doi] LID - e24737 AB - BACKGROUND: Mycobacterium tuberculosis has a global population structure consisting of six main phylogenetic lineages associated with specific geographic regions and human populations. One particular M. tuberculosis genotype known as "Beijing" has repeatedly been associated with drug resistance and has been emerging in some parts of the world. "Beijing" strains are traditionally defined based on a characteristic spoligotyping pattern. We used three alternative genotyping techniques to revisit the phylogenetic classification of M. tuberculosis complex (MTBC) strains exhibiting the typical "Beijing" spoligotyping pattern. METHODS AND FINDINGS: MTBC strains were obtained from an ongoing molecular epidemiological study in Switzerland and Nepal. MTBC genotyping was performed based on SNPs, genomic deletions, and 24-loci MIRU-VNTR. We identified three MTBC strains from patients originating from Tibet, Portugal and Nepal which exhibited a spoligotyping patterns identical to the classical Beijing signature. However, based on three alternative molecular markers, these strains were assigned to Lineage 3 (also known as Delhi/CAS) rather than to Lineage 2 (also known as East-Asian lineage). Sequencing of the RD207 in one of these strains showed that the deletion responsible for this "Pseudo-Beijing" spoligotype was about 1,000 base pairs smaller than the usual deletion of RD207 in classical "Beijing" strains, which is consistent with an evolutionarily independent deletion event in the direct repeat (DR) region of MTBC. CONCLUSIONS: We provide an example of convergent evolution in the DR locus of MTBC, and highlight the limitation of using spoligotypes for strain classification. Our results indicate that a proportion of "Beijing" strains may have been misclassified in the past. Markers that are more phylogenetically robust should be used when exploring strain-specific differences in experimental or clinical phenotypes. FAU - Fenner, Lukas AU - Fenner L AD - Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. lfenner@ispm.unibe.ch FAU - Malla, Bijaya AU - Malla B FAU - Ninet, Beatrice AU - Ninet B FAU - Dubuis, Olivier AU - Dubuis O FAU - Stucki, David AU - Stucki D FAU - Borrell, Sonia AU - Borrell S FAU - Huna, Thembela AU - Huna T FAU - Bodmer, Thomas AU - Bodmer T FAU - Egger, Matthias AU - Egger M FAU - Gagneux, Sebastien AU - Gagneux S LA - eng GR - R01 AI090928/AI/NIAID NIH HHS/United States GR - U01 AI069924/AI/NIAID NIH HHS/United States GR - 5U01-AI069924-5/AI/NIAID NIH HHS/United States GR - R01AI090928-01/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110913 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM MH - *Biological Evolution MH - Genotype MH - Mycobacterium tuberculosis/classification/*genetics MH - Phylogeny MH - Repetitive Sequences, Nucleic Acid/*genetics PMC - PMC3172296 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2011/09/22 06:00 MHDA- 2012/03/01 06:00 PMCR- 2011/09/13 CRDT- 2011/09/22 06:00 PHST- 2011/06/22 00:00 [received] PHST- 2011/08/16 00:00 [accepted] PHST- 2011/09/22 06:00 [entrez] PHST- 2011/09/22 06:00 [pubmed] PHST- 2012/03/01 06:00 [medline] PHST- 2011/09/13 00:00 [pmc-release] AID - PONE-D-11-11180 [pii] AID - 10.1371/journal.pone.0024737 [doi] PST - ppublish SO - PLoS One. 2011;6(9):e24737. doi: 10.1371/journal.pone.0024737. Epub 2011 Sep 13.