A side-by-side comparison of ancient and modern DNA from Mycobacterium leprae—the pathogen responsible for leprosy—shows that the bacterium’s genome and virulence has changed very little over the past 1000 years. The genetic findings suggest that the disease, which was once highly prevalent in Europe, declined primarily because of improved social conditions in the region.
Verena Schuenemann from the University of Tübingen in Tübingen, Germany, along with an international team of colleagues, was able to obtain near-complete genomes of M. leprae from the skeletal remains of five lepers who lived in the United Kingdom, Sweden and Denmark between the 10th and 14th centuries. They then compared those genomes to others that were sequenced from today’s strains of M. leprae.
The researchers’ report, which paints a vivid picture of how the pathogen evolved over the ages, appears in the 14 June issue of Science. Today, despite the availability of effective drugs, leprosy continues to affect about 225,000 people around the world each year.
Once rampant in Medieval Europe, leprosy wreaked havoc on a fearful and superstitious population. Those afflicted were shunned by society and forced to wear bells to broadcast their whereabouts. Then, in the 16th century, cases of the disease began to decline.
Schuenemann and the other researchers used DNA capture techniques and high-throughput sequencing to achieve extraordinary coverage of the ancient M. leprae DNA, taken from the medieval skeletons. They also used recent biopsies from leprosy patients across the globe to obtain a total of 16 ancient and contemporary M. leprae genomes.
The bacterium’s DNA appears to degrade slower than the DNA in human cells, perhaps due to unique protective acids in its thick cell walls, the researchers say.
“Since the M. leprae DNA degrades slower than human—and probably other vertebrate—DNA, it should be possible to extract and sequence M. leprae DNA from environments and time periods in which we would not usually find DNA preserved, like the tropics or early, prehistoric time periods,” said Johannes Krause, a co-author of the Science paper. “So potentially we could study samples from the time of the disease’s origin.”
The researchers’ analysis shows that the M. leprae genome really hasn’t changed much genetically over the millennium: Only about 800 mutations have occurred among the 16 ancient and modern genomes. Based on their findings, Schuenemann and the other researchers also say that different strains of the pathogen found in the Americas probably originated in Europe.
They note that genes in control of the bacterium’s virulence have remained largely intact over the centuries, so they suggest that the decline of leprosy in Europe was most likely due to cleaner living conditions. Other, more opportunistic diseases like plague and tuberculosis may have eclipsed it as well, they said.
“We’ve shown that the mutation rate of leprosy is rather low and that it has not changed much over time,” Krause said. “Therefore, it is less likely to rapidly become antibiotic-resistant. At the same time, constant treatment with antibiotics might still change the genetic makeup of the strains.”
“Two of the [modern] strains show antibiotic-resistant mutations to the drug Dapsone,” Krause continued. “So, when doctors detect this strain in the future, they will already know that the patient should not be treated with Dapsone.”
Given the extremely high quality of their ancient genome sequences, the researchers say that subsequent studies might be able to trace the prehistoric origins of the pathogen.
“The next step will be to go back further in time to understand the adaptation of M. leprae throughout time and to learn about target genes that are essential to the bacterium, which may be targeted by drugs,” Krause said.
Read the abstract, “Genome-Wide Comparison of Medieval and Modern Mycobacterium leprae,” by Verena Schuenemann et al.
Listen to a related Science Podcast.