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Transmission of tuberculosis is linked to historical patterns of human migration

September 27, 2005

St. Petersburg, Russia - Genghis Khan and his troops may have unwittingly used more than just brute military force to conquer entire nations and to establish the infamous Mongolian empire. A report in the October issue of Genome Research suggests that Genghis Khan's invasions spanning the continent of Asia during the 13th century may have been a primary vehicle for the dissemination of one of the world's most deadly diseases: tuberculosis.

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

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

"M. tuberculosis also has a remarkable ability to persist in the human host as a latent, asymptomatic form," explains Mokrousov. "This is probably what permitted M. tuberculosis to co-exist with humans during pre-industrialized times, when the primary mode of transmission was within families or households where there was significant physical contact." Today, approximately one-third of the world's population are carriers of latent TB.

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.

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

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

Cold Spring Harbor Laboratory