title: "Pseudo-Beijing": evidence for convergent evolution in the direct repeat region of Mycobacterium tuberculosis.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. lfenner@ispm.unibe.ch
authors.forename: Lukas
authors.initials: L
authors.lastname: Fenner
authors.forename: Bijaya
authors.initials: B
authors.lastname: Malla
authors.forename: Béatrice
authors.initials: B
authors.lastname: Ninet
authors.forename: Olivier
authors.initials: O
authors.lastname: Dubuis
authors.forename: David
authors.initials: D
authors.lastname: Stucki
authors.forename: Sonia
authors.initials: S
authors.lastname: Borrell
authors.forename: Thembela
authors.initials: T
authors.lastname: Huna
authors.forename: Thomas
authors.initials: T
authors.lastname: Bodmer
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
mesh_terms: D005075:Biological Evolution; D005838:Genotype; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics*; D010802:Phylogeny; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*