Origin and primary dispersal of the Mycobacterium tuberculosis Beijing genotype: Clues from human phylogeography

Abstract

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...

Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese

“…The strains of Bj-MG1 have an intact RD181, whereas all of the other Beijing strains harbor a specific deletion in this region. The strains of Bj-MG3 harbor an insertion of IS6110 in the NTF region and correspond to the previously defined "modern" Beijing subtype (27). Consequently, the Bj-MG1, Bj-MG2, and other Beijing strains correspond to the "ancient" Beijing subtype.…”

“…Previously, a general East Asian/Chinese origin of this strain family was suggested based on its highest prevalence rate and/or highest level of diversity in those regions (18,27,36,50). In the current study, we provided further evidence and proposed a southern East Asia origin of Beijing family, which is consistent with the latest anthropological evidence about the colonization and migrations of modern human in East Asia (39,40).…”

“…The link between drug resistance and the Beijing family has primarily been observed in regions where this family has emerged recently (e.g., Cuba, South Africa, countries of the former Soviet Union) but not in East Asian, where the Beijing family has been endemic for a long time (18,26). Furthermore, more recent studies indicate that the expansion of the Beijing family may have started long before the introduction of vaccination and antibiotic treatment (2,3,27).…”

Presencia del genotipo Beijing entre cepas del complejo Mycobacterium tuberculosis en dos centros de salud de la Región Metropolitana-Chile

“…El genotipo Central-Asia (CAS) o Delhi, localizado en el Medio Oriente, Asia Central, Europa y Australia, lo que lo vincula con los inmigrantes del sur de Asia 1 . El genotipo X, prevalente en América del Norte y regiones de América Central sugiriendo una ascendencia anglosajona o incluso afro-americana 1,6 y por último el genotipo Beijing, endémico y con un claro predominio en ciertas regiones del extremo Oriente, Asia y Oceanía, exceptuando India subcontinental y Sudáfrica 1,8,9 , se ha asociado a alta transmisibilidad, multi-resistencia 8,10 y mayor poder patógeno asociado a la baja inducción de citoquinas inflamatorias, lo que permitiría un mayor crecimiento intracelular del cMtb 2,11 . En los Estados Unidos de América, específicamente en Nueva York, en el año 1991, durante un brote que afectó a ocho pacientes www.sochinf.cl con TBC resistente a isoniacida, rifampicina, etambutol, estreptomicina, kanamicina, etionamida y rifabutina, se identificó el genotipo "W", que fue posteriormente asociado a otros cinco brotes en hospitales del área de Nueva York.…”

Molecular Genotyping of Mycobacterium tuberculosis in Mie Prefecture, Japan, Using Variable Numbers of Tandem Repeats Analysis

“…A recent report suggested that the modern Beijing sublineage, which has high transmissibility, is currently increasing in Japan (12). Furthermore, the modern sublineage is considered to be more virulent and to have higher fitness in human hosts than the ancient sublineage (6,(11)(12)(13). Therefore, it is essential to continuously monitor the population shift for a long period in Mie Prefecture.…”