Transmission Of Tuberculosis Is Linked To Historical Patterns Of Human Migration

In this study, a team of scientists led by Dr. Igor Mokrousov from St.Petersburg's Pasteur Institute demonstrated that the evolutionaryhistory of the causative agent of tuberculosis (TB) has been shaped byhuman migration patterns.

The researchers examined the genetic signatures of over 300 strains of Mycobacterium tuberculosis,rod-shaped bacteria that, when airborne, infect the pulmonary systemsof vulnerable individuals and give rise to clinical TB. The WorldHealth Organization (WHO) estimates that TB kills 5,000 peopleworldwide every day, or approximately 2 million people each year. Thepathogen is rapidly spreading and evolving multi-drug resistant strainsin susceptible regions such as Africa. Interestingly, a strong genderbias in TB infection is reported globally each year; a 70% excess ofmale TB cases is typical.

"M. tuberculosis also has aremarkable ability to persist in the human host as a latent,asymptomatic form," explains Mokrousov. "This is probably whatpermitted M. tuberculosis to co-exist with humans duringpre-industrialized times, when the primary mode of transmission waswithin families or households where there was significant physicalcontact." Today, approximately one-third of the world's population arecarriers of latent TB.

Mokrousov's team hypothesized that, given the strong gender bias of TBinfectivity and the likely family-based mode of TB transmission duringpre-industrialized times, M. tuberculosisdissemination has reflected the unidirectional inheritance of thepaternally transmitted human Y chromosome. To test this hypothesis, theauthors compared the genetic profiles of a common form of M. tuberculosis,called the Beijing genotype, with known patterns of prehistoric andrecent human migrations, as well as with global patterns ofY-chromosome variation. Strikingly, they observed that over the past60,000-100,000 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. tuberculosisoriginated in a specific human population called the K-M9 in centralAsia approximately 30,000-40,000 years ago following a second "out ofAfrica" migration event. The bacteria and its human host thendisseminated northeast into Siberia between 20,000-30,000 years ago andthroughout eastern Asia between 4,000-10,000 years ago. More recently,the Beijing genotype of M. tuberculosis was introduced intonorthern Eurasia, perhaps by Genghis Khan himself during the 1200's,and into South Africa, possibly through sea trade contacts withIndonesia or China during the last 300 years.

"The population structure of M. tuberculosisappears to have been shaped by the demographic history of its humancarrier," explains Mokrousov, "but this is the opposite of what WilliamMcNeill suggested in 1976 in his famous book Plagues and Peoples,where he so popularly described how the growth and spread of infectiousdiseases such as the Black Death have influenced human history."

Mokrousov feels that these observations have important implications fortracing the evolutionary history of microorganisms. "The timing ofhallmark changes in bacterial genomes within the last 100,000 years maybe inferred from comparison with relevant human migrations," he says.