Background: The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database.

The present update on the global distribution of Mycobacterium tuberculosis complex spoligotypes provides both the octal and binary descriptions of the spoligotypes for M. tuberculosis complex, including Mycobacterium bovis, from >90 countries (13,008 patterns grouped into 813 shared types containing 11,708 isolates and 1,300 orphan patterns). A number of potential indices were developed to summarize the information on the biogeographical specificity of a given shared type, as well as its geographical spreading (matching code and spreading index, respectively). To facilitate the analysis of hundreds of spoligotypes each made up of a binary succession of 43 bits of information, a number of major and minor visual rules were also defined. A total of six major rules (A to F) with the precise description of the extra missing spacers (minor rules) were used to define 36 major clades (or families) of M. tuberculosis. Some major clades identified were the East African-Indian (EAI) clade, the Beijing clade, the Haarlem clade, the Latin American and Mediterranean (LAM) clade, the Central Asian (CAS) clade, a European clade of IS6110 low banders (X; highly prevalent in the United States and United

We present a short summary of recent observations on the global distribution of the major clades of the Mycobacterium tuberculosis complex, the causative agent of tuberculosis. This global distribution was defined by data-mining of an international spoligotyping database, SpolDB3. This database contains 11,708 patterns from as many clinical isolates originating from more than 90 countries. The 11,708 spoligotypes were clustered into 813 shared types. A total of 1,300 orphan patterns (clinical isolates showing a unique spoligotype) were also detected.

We suggest that the evolution of the population structure of microbial pathogens is influenced by that of modern humans. Consequently, the timing of hallmark changes in bacterial genomes within the last 100,000 yr may be attempted by comparison with relevant human migrations. Here, we used a lineage within Mycobacterium tuberculosis, a Beijing genotype, as a model and compared its phylogeography with human demography and Y chromosome-based phylogeography. We hypothesize that two key events shaped the early history of the Beijing genotype: (1) its Upper Palaeolithic origin in the Homo sapiens sapiens K-M9 cluster in Central Asia, and (2) primary Neolithic dispersal of the secondary Beijing NTFϻIS6110 lineage by Proto-Sino-Tibetan farmers within east Asia (human O-M214/M122 haplogroup). The independent introductions of the Beijing strains from east Asia to northern Eurasia and South Africa were likely historically recent, whereas their differential dissemination within these areas has been influenced by demographic and climatic factors.[Supplemental material is available online at www.genome.org.]Intriguing clues about the history of a biological species can be derived from the study of the geographical distribution of the phylogenetic/genealogical lineages, in the approach known as "phylogeography" (Avise et al. 1987). The underlying assumption of human phylogeography is that there is a correspondence between the overall distribution of haplotypes and haplogroups and past human movements. The uniparentally inherited nonrecombining haploid mtDNA and the Y chromosome loci are particularly sensitive to the influences of drift, especially founder effect. Consequently these loci are suitable for assessing the origins of contemporary population diversity and provide context for paleontological hypothesis testing (Foley 1998). The mutation rate of the maternally transmitted mitochondrial genome is ∼10 times higher than that of nuclear DNA, which provides abundance of polymorphic sites but creates difficulties in reconstructing genealogies owing to repeated and reverse mutations. By contrast, the mutation rate of the paternally inherited nonrecombining portion of the Y chromosome (NRY) is comparable to that of nuclear DNA, which means that polymorphisms are more difficult to find but genealogies are easier to reconstruct. In addition, the greater length of the NRY DNA compared with mtDNA compensates in data analysis for its lower mutation rate (Cavalli-Sforza and Feldman 2003).The rarity of back and recurrent mutations in NRY contributes to the property of displaying the strongest geographic correlation and greatest diversity among, rather than within, populations. To date, NRY binary polymorphisms have been widely used to trace the origin and migration events of modern humans (Underhill et al. 2001). Here, we propose the hypothesis that NRY-based phylogeography of H. sapiens sapiens, offers a convenient spatiotemporal framework for inferring early primary dispersals of those human pathogens that are essentially (1) devo...

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