Long before the Black Death or AIDS ravaged society, there was leprosy. Now, the first comprehensive genetic comparison of the bacterial strains that cause the disease is shedding light on where leprosy originated and how it has followed people seemingly everywhere they've gone.
Confirmed reports of leprosy first appear around 600 B.C.E. in sacred Indian texts that describe a victim's loss of finger and toe sensation, a hallmark of the damage the bacterium Mycobacterium leprae inflicts on the nervous system. By Medieval times, cultures around the globe were familiar with the deforming lesions and decaying flesh that resulted in lepers being burned at the stake or carted off to die in remote colonies. Antibiotics helped bring the disease under control in the 1940s, but it persists in poor regions, and there are more than 500,000 new cases reported each year.
To understand how the disease spread across the globe, molecular microbiologist Stewart Cole of the Pasteur Institute in Paris and colleagues compared genomes among seven M. leprae strains culled from various countries. To their surprise, the strains had practically identical genomes, indicating that one clone had essentially infected the entire world.
Upon closer examination, the team found subtle DNA sequence mutations called single nucleotide polymorphisms that allowed them to break a total of 175 worldwide strains into four types. Most Central Asian strains are of the type-1 variety, whereas type 2 predominates in Ethiopia, type 3 in Europe, North Africa, and the Americas, and type 4 in West Africa and the Caribbean. The mutation patterns among the strains suggest that leprosy originated in either Central Asia or East Africa, says Cole, whose group publishes its findings 13 May in Science. "India has been stigmatized as the cradle of leprosy," he says. "But the disease could have just as likely arisen in East Africa." Another striking finding is the apparent effect of European emigration and the West African slave trade on the spread of leprosy. M. leprae types 3 and 4 are more similar to each other than they are to type 1, indicating that these activities, rather than human passage from Asia via the Bering Strait, brought the disease to the New World.
"It's very interesting work that should help us fill in the picture of how human migration is tied to the dissemination of leprosy," says Daniel Hartl, a population geneticist at Harvard University. But molecular anthropologist Connie Mulligan of the University of Florida, Gainesville, says the researchers need more genetic evidence to pinpoint the origin of the disease.