September 27, 2005

The spread of tuberculosis

Genghis Khan's previous claim to genetic fame was linked to the presence in about 0.5% of the population of the entire world and in a substantial portion of the population of Central Asia, of a unique Y-chromosome haplotype.

Now, a team of geneticists led by Igor Mokrusov are uncovering the darker aspects of the Great Khan's conquests. From their press release.
Mokrousov's team hypothesized that, given the strong gender bias of TB infectivity and the likely family-based mode of TB transmission during pre-industrialized times, M. tuberculosis dissemination has reflected the unidirectional inheritance of the paternally transmitted human Y chromosome. To test this hypothesis, the authors compared the genetic profiles of a common form of M. tuberculosis, called the Beijing genotype, with known patterns of prehistoric and recent human migrations, as well as with global patterns of Y-chromosome variation. Strikingly, they observed that over the past 60,000-100,000 years, the dispersal and evolution of M. tuberculosis appears to have precisely ebbed and flowed according to human migration patterns.

The authors describe how the Beijing genotype of M. tuberculosis originated in a specific human population called the K-M9 in central Asia approximately 30,000-40,000 years ago following a second "out of Africa" migration event. The bacteria and its human host then disseminated northeast into Siberia between 20,000-30,000 years ago and throughout eastern Asia between 4,000-10,000 years ago. More recently, the Beijing genotype of M. tuberculosis was introduced into northern Eurasia, perhaps by Genghis Khan himself during the 1200's, and into South Africa, possibly through sea trade contacts with Indonesia or China during the last 300 years.

Please note that while most news will doubtlessly focus on the Genghis Khan angle, the spread of haplogroup K-M9 occurred in deep prehistory. Only much later did a a particular genotype of M. tuberculosis spread, perhaps by the actions of Genghis Khan, although there have been multiple incursions of Mongoloid peoples which may account for the current distribution, and as the authors note, its introduction into South Africa was an independent event.


I have finished reading the paper, and the argument that the authors make for the introduction of the variant in Europe by the armies of Genghis Khan is quite ingenuous:
Since the Beijing genotype is not a European endemic variant, the published PC analysis of European human populations allows us to rule out those migrations that equally concerned both Russia and Europe as sources of the Beijing strains. These are defined by Finno-Ugric (PC2) (Cavalli-Sforza 2001), Scythe (PC3) (Cavalli-Sforza 2001), and Hun (Christian 1998) expansions. We may further speculate that trade contacts as such, even long-lasting ones, are not sufficient for an effective dissemination of the M. tuberculosis strains if they are not supported by a kind of demic diffusion of the strains’ carriers, manifested as population growth and migration. The Silk Road connected China with Europe for almost two millennia, 2 BC–1600 AD (Christian 1998), and this route may have been opened much earlier, based on the transfer of the first ceramics technology from Japan to the Middle East and Europe at the beginning of agricultural practice (Cavalli-Sforza 2001). However, it is appropriate to reiterate that Beijing strains are not identified as a European endemic variant.

Finally, we suggest the TB spread related to the Genghis (or Chinggiz) Khan invasion to be more plausible. The Mongol empire of the 13th century brought the different parts of Eurasia closer than they had ever been before and created an economic and cultural system embracing much of the Eurasian land mass (Christian 1998). It was also a period of remarkable ethnic mixing since the Mongol army grew by incorporating the armies of many different nations that it had defeated, including Han Chinese (Christian 1998). McNeill (1976) suggested that Mongol invasions also unified Eurasia epidemiologically, allowing the exchange of the disease vectors throughout Eurasia. Genghis Khan did eventually come in the center of Europe, but for a short time. This was sufficient for the dissemination of Yersinia pestis to occur, but not for that of the far less contagious M. tuberculosis. Even if some M. tuberculosis Beijing genotype strains had been brought to Europe in this way, this may not have manifested rapidly. Subsequently, the Black Death that decimated European human populations could have efficiently eliminated rare carriers of the M. tuberculosis Beijing genotype. By contrast, further close interaction between Rus’ and Orda was prolonged for three centuries, and it may be possible that the Mongol invasion and the subsequent yoke/cohabitation were indeed the vehicle that brought M. tuberculosis Beijing genotype strains to Russia
The authors are noting that there have been multiple movements of peoples from Asia to Europe. So, how do they conclude that the Mongols of Genghis Khan are implicated? If the genotype was brought e.g., by the Huns, or the Scythians, or the Finno-Ugrians, then we would expect to find it commonly in Europe, because these movements affected large parts of the continent. But, the Beijing haplotype is not a European variant, so by a process of elimination these movements are probably not responsible for its dissemination.

Rather, it is the Mongols who held Russia -but not Europe- captive for three centuries, and Russia is the country in Europe where the Beijing genotype is found. Moreover, since the Mongols recruited soldiers from China, they could have acquired the genotype, and then brought it to Russia. It is then during the centuries of Mongol domination, at the western edge of Mongol expansion that the Beijing genotype was brought to Russia.

Genome Research

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

Igor Mokrousov et al.


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 NTF::IS6110 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.


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