Gene study challenges theory of leprosy’s origin

Mycobacterium leprae (red) Copyright: CDC

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A study comparing the genes of different strains of the bacterium responsible for leprosy challenges the theory that it originated in India and spread to Europe along with Alexander the Great’s returning troops.

The study, led by Stewart Cole at the Pasteur Institute in Paris, France, collected strains of Mycobacterium leprae from around the world, and compared their genes to trace the historical spread of the disease.

The results, published in this week’s issue of Science, show that the different strains turned out to be strikingly similar. This indicates that the genes have been transmitted through the centuries with remarkably few changes.

The research shows that the bacterium seems to have adapted to become more specialised. Its genome has become ‘impoverished’, losing several genes for important functions such as respiration.

Mark Thomas, a population geneticist at University College London in the United Kingdom, explains that the bacterium relies on the host it infects to fulfil these functions.

In theory, this specialisation could be important for developing new drugs and vaccines to break through the bacterium’s armour.

Genes generally evolve with time to create a range of genetically diverse organisms. But, after its initial ‘downsizing’, the leprosy genome seems to have remained stable.

It was only when the researchers looked at small-scale changes in DNA that they were able to identify enough genetic differences to divide their samples into four different types.

Type 1 was mostly seen in Central Asia; type 2 in Ethiopia; type 3 in Europe, North Africa and the Americas; and type 4 in West Africa and the Caribbean.

Leprosy was first recorded around 600 BC in ancient Indian texts that mentioned its existence in China, India and Egypt.

It is thought to have originated in India — which now has 70 per cent of the world’s cases — and spread from there to China and Japan, and to Europe, carried by Alexander the Great’s troops returning from India.

Marc Monot, a member of the research team, told SciDev.Net that their findings contradict this widely held theory. Leprosy most probably originated in either East Africa or Central Asia, he says, and “then extended its reach to the east and west in a pattern mirroring human migration”.

Of the two proposed regions of origin, East Africa is most likely, says Monot. He explains that the East African strain seems to be the rarest, which in population genetics terms marks it is as the oldest.

The study suggests that the disease would have reached North America and West Africa through infected explorers, traders or colonialists some time in the past 500 years, and that it infiltrated the Caribbean and South America via the slave trade in the 18th century.

Monot adds that the main strain in the Americas most closely resembles that in Europe and North Africa, suggesting that colonists to the New World brought “unwanted Old World souvenirs” with them.

Thomas explains that the relatively recent spread of the disease — over the last 4000 years or so — fits with the fact that the genome is similar in different parts of the world.

In poor countries of Africa, Asia and Latin America, leprosy is still considered a public health problem in by the World Health Organization. It is treatable, but more effort is needed to eliminate it.

The disease affects the skin and nerves. If left untreated, it can permanently damage them, along with the limbs and eyes.

The disease is disfiguring, and the stigma associated with it is thought to be a major barrier for patients reporting the disease themselves and seeking early treatment.

Last year, the United Nations pledged to investigate the issues of social discrimination and human rights violations against sufferers and their families.

The team’s findings have relevance to tackling the disease, says Monot. Because all the bacteria that cause leprosy have a very similar genome, drugs and vaccines against the disease should work “universally”.

Link to full paper by M. Monot et al in Science

Reference: Science 308, 1040 (2005)