History and Phylogeography of Leprosy

Leprosy results from infection with Mycobacterium leprae, an unculturable pathogen with an exceptionally long generation time that has afflicted human populations for millenia. The history of leprosy has been documented by various civilizations and its global spread deduced from the anthropological record, although scientific proof for the latter is often lacking. Considerable insight into the biology, genetics, and evolution of the leprosy bacillus has been obtained from genomics. M. leprae has undergone extensive reductive evolution, losing DNA from its genome, half of which is now occupied by pseudogenes. Comparative genomics of four different strains from India, Brazil, Thailand, and the USA revealed remarkable conservation of the ~3.27-megabase genome (99.995% identity) yet uncovered 215 polymorphic sites, mainly single-nucleotide polymorphisms (SNP), and a handful of new pseudogenes. Mapping these polymorphisms in a large panel of strains defined 16 SNP subtypes that showed strong geographical associations and helped retrace the evolution of M. leprae and the dissemination of leprosy.