Insight into the evolution and origin of leprosy bacilli from the genome sequence of <i>Mycobacterium lepromatosis</i>

Significance Leprosy was thought to be exclusively caused by infection of humans by Mycobacterium leprae . In 2008, Han et al. proposed that Mycobacterium lepromatosis , a separate unculturable species, might be responsible for a rare yet severe form of the disease called diffuse lepromatous leprosy. Here, by using comparative genomics, we show that the two species are very closely related and derived from a common ancestor that underwent genome downsizing and gene decay. Since their separation 13.9 Mya, the two species have continued to lose genes, but from different regions of the genome, and M. leprae appears to be more recent. In a phylogeographic survey, by using differential PCR, we found that M. lepromatosis was scarce and restricted to patients from Mexico.