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Ancient Leprosy Analysis Suggests High Pathogen Genetic Diversity in Medieval Europe

NEW YORK (GenomeWeb) – A new study of ancient DNA suggests the leprosy-causing pathogen Mycobacterium leprae has been circulating in Europe for more than 1,500 years, perhaps originating on the continent.

Through an analysis of 10 Medieval age M. leprae genomes from skeletons across Europe, researchers from the University of Tübingen, the University of Zurich, and elsewhere identified four M. leprae branches in Europe during the early medieval period and three more branches from a cemetery representing a later point in the Middle Ages. The findings, reported online today in PLOS Pathogens, dramatically increases the M. leprae genetic diversity documented in Europe during medieval times.

"We found much more genetic diversity in ancient Europe than expected," cosenior author Johannes Krause, an archeological sciences and archeogenetics researcher affiliated with the University of Tübingen and the Max Planck Institute for the Science of Human History, said in a statement. "[W]e found that all known strains of leprosy are present in Medieval Europe, suggesting that leprosy may already have been widespread throughout Asia and Europe in antiquity or that it might have originated western Eurasia."

Although leprosy was particularly common in 16th century Europe, the disfiguring infectious disease was documented long before. It persists in some parts of the world even today, though the reasons for its rising and waning prevalence over time — and its historical origins — are not well understood.

"Characterization and geographic association of the most ancestral strains are crucial for deciphering leprosy's exact origin," cofirst author Verena Schuenemann, an archeological sciences researcher at the University of Tübingen and University of Zurich, said in a statement. "While we have some written records of leprosy cases that predate the Common Era, none of these have yet been confirmed on a molecular level."

For a paper appearing in Science in 2013, Krause and his colleagues compared genome sequence patterns in five medieval leprosy pathogens with those present in 11 modern M. leprae strains, uncovering several M. leprae branches despite general genomic conservation over time. In a paper published in Nature Communications earlier this month, on the other hand, members of the same team focused on the human side of the equation, describing human leukocyte antigen alleles suspected of influencing medieval individuals' susceptibility to the disfiguring infectious disease.

For this new study, the team used PCR, shotgun sequencing, or bead capture sequencing to screen for M. leprae DNA in dozens of skeletal samples from sites in Denmark, Italy, Hungary, the Czech Republic, and the UK that showed signs of potential leprosy infection, including skeletal deformities.

By doing whole-genome enrichment and sequencing on the M. leprae-positive samples, the researchers successfully generated at least sevenfold average coverage for 10 of the European pathogens, ranging in age from about 700 to more than 1,500 years old.

Their phylogenetic analysis — which included the newly sequenced strains, sequences for seven medieval M. leprae isolates analyzed in the past, and 142 modern leprosy genomes — led to more than 3,100 SNPs.

Each of the four isolates from the early medieval period fell into its own branch, the team noted, while three more M. leprae branches were unearthed at a Danish cemetery with remains from the more recent high medieval period, significantly boosting the diversity of leprosy strains identified in Europe during this stretch of history.

"The resulting more complex picture of the past phylogeography of leprosy in Europe impacts current phylogeographical models of M. leprae dissemination," the authors wrote, noting that the current findings "highlight how studying ancient M. leprae strains improves understanding the history of leprosy worldwide."