The completion of the Mycobacterium leprae genome sequence, which has now been published in Nature 1xMassive gene decay in the leprosy bacillus. Cole, S.T et al. Nature. 2001; 409: 1007–1011Crossref | PubMed | Scopus (1048)See all References1, is a landmark event, as this bacterium, discovered by Armauer G. Hansen as the causative organism for leprosy in 1873, was the first bacterial pathogen to be identified as the cause of a human infectious disease.Leprosy is a chronic infectious disease that has existed since the dawn of civilization and is still a major public health problem. Clinically, severe peripheral neuropathies underlie the sensorimotor loss that accounts for most of the deformities and disabilities associated with leprosy. Although WHO-introduced multidrug therapy has dramatically reduced the number of leprosy patients worldwide, the detection of new cases in endemic areas has not been reduced. Lack of understanding of the basic biology of M. leprae has thus far been the key to the failure of leprosy research to advance. Now, the completion of the genome sequence will enable testing of hypotheses that have immediate practical applications, such as drug discovery, diagnostic tools and vaccines.The M. leprae genome is 3.3 Mb, circular and has an average G+C content of 57.8%. Comparison with its close relative, Mycobacterium tuberculosis reveals that M. leprae might have lost ∼2000 genes from its common mycobacterial ancestor. Only 49.5% of the M. leprae genome contains functional genes and 27% are translationally inert psuedogenes with inactive reading frames. The remaining 23.5% do not seem to be coding, probably because of mutation. This raises questions as to why and how a bacterial chromosome retains non-functional DNA. Hopefully, future comparative genomic studies will provide clues.In spite of this reductive evolution, M. leprae appears to have preserved the most vital genes among the active 1604 genes that are required for its obligatory parasitism. Compared with M. tuberculosis, M. leprae has lost crucial metabolic activities and their regulatory pathways, which probably explains why attempts to culture it in vitro have failed. The genome sequence also sheds new light on its extensive capabilities for lipid metabolism and fatty acid degradation. Several genes that encode key enzymes for the synthesis of structural components of the mycobacterial cell wall and fatty acid degradation, which are functional in M. tuberculosis, are missing or inactive in M. leprae. However, M. leprae has several enzymes that have no counterparts in M. tuberculosis, and there are unique genes with no orthologue in M. tuberculosis. Considering the entirely different pathology and tissue specificity of these two mycobacterial species, the differences in their genomes were not unexpected; however, the role of these differences in the pathogenesis of leprosy is presently unknown.The complete sequence of the M. leprae genome will provide the foundation of future research and will be invaluable in understanding the molecular basis for the complicated pathogenic mechanisms of leprosy. Moreover, the use of comparative genomics of mycobacterial species will reveal the history of molecular evolution and enable us to understand how the genes of M. leprae and M. tuberculosis function in completely different pathological settings.