02133nas a2200397   4500000000100000008004100001260001300042653002500055653002100080653002200101653001100123653001200134653002500146100001600171700001500187700001400202700001400216700001300230700001400243700001400257700001400271700001600285700001600301700001500317700001300332700001400345700001600359700001300375245004900388856005900437300001100496490000700507050003200514520117500546022001401721       2001                            d  c2001 Dec10aEvolution, Molecular10aGenes, Bacterial10aGenome, Bacterial10aHumans10aleprosy10aMycobacterium leprae1 aEiglmeier K1 aParkhill J1 aHonoré N1 aGarnier T1 aTekaia F1 aTelenti A1 aKlatser P1 aJames K D1 aThomson N R1 aWheeler P R1 aChurcher C1 aHarris D1 aMungall K1 aBarrell B G1 aCole S T00aThe decaying genome of Mycobacterium leprae.  uhttp://leprev.ilsl.br/pdfs/2001/v72n4/pdf/v72n4a02.pdf  a387-980 v72  aInfolep Library - available3 a<p>Everything that we need to know about Mycobacterium leprae, a close relative of the tubercle bacillus, is encrypted in its genome. Inspection of the 3.27 Mb genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus identified 1,605 genes encoding proteins and 50 genes for stable RNA species. Comparison with the genome sequence of Mycobacterium tuberculosis revealed an extreme case of reductive evolution, since less than half of the genome contains functional genes while inactivated or pseudogenes are highly abundant. The level of gene duplication was approximately 34% and, on classification of the proteins into families, the largest functional groups were found to be involved in the metabolism and modification of fatty acids and polyketides, transport of metabolites, cell envelope synthesis and gene regulation. Reductive evolution, gene decay and genome downsizing have eliminated entire metabolic pathways, together with their regulatory circuits and accessory functions, particularly those involved in catabolism. This may explain the unusually long generation time and account for our inability to culture the leprosy bacillus.</p>  a0305-7518