70,000 years of TB infection and evolution

01 September 2013

Mycobacterium tuberculosis.

Image: Mycobacterium tuberculosis. Transmission electron micrograph (TEM) of Mycobacterium tuberculosis bacteria. It is a rod- shaped bacillus that causes tuberculosis (TB) in humans.©  PASIEKA/SCIENCE PHOTO LIBRARY

Tuberculosis (TB) infected early humans in Africa 70,000 years ago and was carried worldwide by human out-of-Africa migrations, according to new research into the genome sequences of Mycobacterium tuberculosis, the bacteria responsible for the disease. 

Douglas Young of the MRC's National Institute for Medical Research (now part of the Francis Crick Institute)  worked with an international team to identify changes over that time in the genome. These changes caused TB to become a more aggressive disease. The work is hoped to lead to new targets for drug treatment. 

Dr Young explained: "The number of tuberculosis bacteria increased markedly in association with human population expansion during the Neolithic revolution, perhaps adapting to cause a more virulent form of disease. 

"If we are correct in inferring that TB has moved from a predominantly latent infection to a more aggressive disease, identification of underlying changes in the bacterial genome may uncover novel targets for drug development." 

Dr Young and his team used high-throughput DNA sequencing techniques to analyse the whole genomes of 259 strains of M. tuberculosis. They then used a series of statistical tools and methods for analysing biological data to construct a model of how the bacterium evolved and to set this within a geographic and historical context. 

They suggest that the long history of M. tuberculosis evolving alongside humans (for 70,000 years) shows that it has been able to adapt to changing human populations during this time - including both low and high population densities. Diseases infecting high density populations tend to be highly infectious and easily transmitted, relying on large populations to make sure the disease doesn't become extinct, while diseases infecting low density populations survive using characteristics such as periods of latency followed by reactivation. M. Tuberculosis has evolved to show both patterns. 

Dr Young concluded: "A potential implication of this line of research is the identification of strains of tuberculosis bacteria that differ in the threat they pose to public health. This may contribute to future drug discovery and to the design of improved strategies for disease control."

He added: "The idea that TB has co-evolved with modern humans throughout our history of migration and population expansion is of fundamental interest in our efforts to understand the human condition. Tracking events affecting evolution of the bacteria may provide novel insights into events in our own prehistory."

The paper, Out-of-Africa migration and Neolithic co-expansion of Mycobacterium tuberculosis with modern humans, is published in Nature Genetics.

  • Researchers have modelled the evolutionary history of the bacterium responsible for tuberculosis (TB). They have shown that it emerged in early humans around 70,000 years ago and has evolved alongside humans to adapt to changing populations over that time. Changes in the TB bacterium's genome over that time have caused it to become a more aggressive disease. 
  • According to the WHO, these days TB is second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent. In 2011, it killed 1.4 million people and caused illness in 8.7 million. 
  • The Neolithic revolution, when the number of TB bacteria increased significantly, is also known as the first agricultural revolution and is thought to have begun around 12,000 years ago. Human population density increased significantly at this time.