RESUMO
Leprosy, a chronic human disease with potentially debilitating neurological consequences, results from infection with Mycobacterium leprae. This unculturable pathogen has undergone extensive reductive evolution, with half of its genome now occupied by pseudogenes. Using comparative genomics, we demonstrated that all extant cases of leprosy are attributable to a single clone whose dissemination worldwide can be retraced from analysis of very rare single-nucleotide polymorphisms. The disease seems to have originated in Eastern Africa or the Near East and spread with successive human migrations. Europeans or North Africans introduced leprosy into West Africa and the Americas within the past 500 years.
Assuntos
Emigração e Imigração , Hanseníase/história , Mycobacterium leprae/genética , África/epidemiologia , América/epidemiologia , Ásia/epidemiologia , Evolução Biológica , Europa (Continente)/epidemiologia , Genes Bacterianos , Genoma Bacteriano , História do Século XVIII , História do Século XIX , História Antiga , História Medieval , Humanos , Sequências Repetitivas Dispersas , Hanseníase/epidemiologia , Hanseníase/microbiologia , Hanseníase/transmissão , Repetições Minissatélites , Mycobacterium leprae/classificação , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Dinâmica Populacional , Pseudogenes , Análise de Sequência de DNARESUMO
Leprosy, a chronic human disease with potentially debilitating neurological consequences, results from infection with Mycobacterium leprae. This unculturable pathogen has undergone extensive reductive evolution, with half of its genome now occupied by pseudogenes. Using comparative genomics, we demonstrated that all extant cases of leprosy are attributable to a single clone whose dissemination worldwide can be retraced from analysis of very rare single-nucleotide polymorphisms. The disease seems to have originated in Eastern Africa or the Near East and spread with successive human migrations. Europeans or North Africans introduced leprosy into West Africa and the Americas within the past 500 years.
Assuntos
Humanos , História Antiga , História Medieval , História do Século XVIII , História do Século XIX , Ásia/epidemiologia , América/epidemiologia , Pseudogenes , Genoma Bacteriano , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , África/epidemiologia , Emigração e Imigração , Europa (Continente)/epidemiologia , Genes Bacterianos , Hanseníase/história , Hanseníase/microbiologia , Hanseníase/transmissão , Hanseníase/epidemiologia , Mycobacterium leprae/classificação , Mycobacterium leprae/genéticaRESUMO
Mycobacterium bovis is the causative agent of tuberculosis in a range of animal species and man, with worldwide annual losses to agriculture of $3 billion. The human burden of tuberculosis caused by the bovine tubercle bacillus is still largely unknown. M. bovis was also the progenitor for the M. bovis bacillus Calmette-Guérin vaccine strain, the most widely used human vaccine. Here we describe the 4,345,492-bp genome sequence of M. bovis AF2122/97 and its comparison with the genomes of Mycobacterium tuberculosis and Mycobacterium leprae. Strikingly, the genome sequence of M. bovis is >99.95% identical to that of M. tuberculosis, but deletion of genetic information has led to a reduced genome size. Comparison with M. leprae reveals a number of common gene losses, suggesting the removal of functional redundancy. Cell wall components and secreted proteins show the greatest variation, indicating their potential role in host-bacillus interactions or immune evasion. Furthermore, there are no genes unique to M. bovis, implying that differential gene expression may be the key to the host tropisms of human and bovine bacilli. The genome sequence therefore offers major insight on the evolution, host preference, and pathobiology of M. bovis.