03074nas a2200829 4500000000100000008004100001260001600042653001200058653001500070653001900085653002200104653002500126653003000151653002200181653001100203653001200214653002800226653002100254653002500275653002700300100001300327700001600340700001500356700001400371700001600385700001600401700001400417700001400431700001500445700001300460700001400473700001300487700001200500700002000512700001300532700001500545700001300560700001300573700001500586700001300601700001300614700001400627700001400641700001300655700001400668700001400682700001200696700001300708700001300721700001400734700001900748700001900767700001300786700001300799700001200812700001500824700001400839700001400853700001400867700001400881700001300895700001600908700001700924700001600941245004800957856007001005300001201075490000801087050001401095520112101109022001402230 2001 d c2001 Feb 2210aAnimals10aArmadillos10aDNA, Bacterial10aEnergy Metabolism10aEvolution, Molecular10aGene Transfer, Horizontal10aGenome, Bacterial10aHumans10aleprosy10aMolecular Sequence Data10aMultigene Family10aMycobacterium leprae10aSequence Analysis, DNA1 aCole S T1 aEiglmeier K1 aParkhill J1 aJames K D1 aThomson N R1 aWheeler P R1 aHonoré N1 aGarnier T1 aChurcher C1 aHarris D1 aMungall K1 aBasham D1 aBrown D1 aChillingworth T1 aConnor R1 aDavies R M1 aDevlin K1 aDuthoy S1 aFeltwell T1 aFraser A1 aHamlin N1 aHolroyd S1 aHornsby T1 aJagels K1 aLacroix C1 aMaclean J1 aMoule S1 aMurphy L1 aOliver K1 aQuail M A1 aRajandream M A1 aRutherford K M1 aRutter S1 aSeeger K1 aSimon S1 aSimmonds M1 aSkelton J1 aSquares R1 aSquares S1 aStevens K1 aTaylor K1 aWhitehead S1 aWoodward J R1 aBarrell B G00aMassive gene decay in the leprosy bacillus. uhttp://www.nature.com/nature/journal/v409/n6823/pdf/4091007a0.pdf a1007-110 v409 aCOLE 20013 a

Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.

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