Tübingen-led scientists reconstruct the complete historical genome of medieval and ancient scourge
An international team of scientists reconstructed a dozen medieval and modern leprosy genomes – suggesting a European origin for the North American leprosy strains found in armadillos and humans, and a common ancestor of all leprosy bacteria within the last 4000 years.
It is the first time scientists have reconstructed an ancient genome without a reference sequence (de novo) due to the extraordinary preservation of the medieval pathogen’s DNA. This finding indicates that ancient bacterial DNA may survive in some cases much beyond the one million year boundary suggested for vertebrate DNA.
Leprosy, a devastating chronic disease caused by the bacterial pathogen Mycobacterium leprae, was prevalent in Europe until the late Middle Ages. Today, the disease is found in 91 countries worldwide with about 200,000 new infections reported annually.
To retrace the history of the disease, an international team of scientists, led by Johannes Krause from Tübingen University and Stewart Cole from EPFL Lausanne, have reconstructed entire genome sequences of M. leprae bacteria from five medieval skeletons that were excavated in Denmark, Sweden and the United Kingdom as well as seven biopsy samples from modern patients.
The researchers compared the medieval European M. leprae genomes with 11 worldwide modern strains, including the seven biopsy strains, revealing that all M. leprae strains share a common ancestor that existed within the last 4000 years. This is congruent with the earliest osteological evidence for the disease in the archaeological records dated to 2000 BC from India. The genome comparisons indicate a remarkable genomic conservation of the bacteria during the past 1,000 years. The team of scientists could furthermore show that M. leprae genotypes in medieval Europe are today found in the Middle East, whereas other medieval strains show a striking similarity to modern strains found today in North American armadillos and leprosy patients suggesting a Eu-ropean origin of leprosy in the Americas.
One skeleton from Denmark (Jorgen 625) showed extraordinary preservation of the pathogen DNA, allowing a genome reconstruction without using a modern reference sequence, which was never done before for an ancient organism’s genome. The scientists found that almost half of the DNA recovered from that particular specimen derived from M. leprae bacteria; this is orders of magnitude higher than the amount of pathogen DNA usually observed in skeletons and modern patients. They furthermore found that the M. leprae DNA was far better preserved compared to the human DNA, which may explain this unusually high amounts of bacterial DNA in these skeleton samples.
According to the authors this may be due to the extremely thick and impervious waxy cell wall of the leprosy bacillus that protects their DNA from degradation. Therefore, the authors speculate that some bacterial DNA may be preserved much longer than any vertebrate DNA, which is usually less protected. “This opens the possibility that certain types of bacterial DNA may survive well beyond the maximum age for mammalian DNA of around one million years,” says Krause and adds, “This gives us a real perspective to trace back the pre-historic origins of a disease.”