title: Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome.
abstract: The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. leprae genome sequence to approximately 66% completion. The sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 tRNAs, and 15 tRNAs. The gene density of one per 1.4 kb is slightly lower than that of Mycoplasma (1.2 kb). Of the protein coding genes, 44% have significant matches to genes with well-defined functions. Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins shows a complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall, cell division, multidrug resistance, and virulence proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.
authors.affiliation: Genome Therapeutics Corporation, Collaborative Research Division, Waltham, Massachusetts 02154, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Smith
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authors.lastname: Richterich
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authors.lastname: Rubenfield
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authors.lastname: Gundersen
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authors.lastname: Falls
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authors.lastname: Imrich
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authors.lastname: Torrey
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authors.lastname: Engelstein
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authors.lastname: Breton
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authors.lastname: Madan
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authors.lastname: Nietupski
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authors.lastname: Seitz
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authors.lastname: Connelly
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authors.lastname: McDougall
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authors.lastname: Safer
authors.forename: R
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authors.lastname: Gibson
authors.forename: L
authors.initials: L
authors.lastname: Doucette-Stamm
authors.forename: K
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authors.lastname: Eiglmeier
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authors.lastname: Bergh
authors.forename: S T
authors.initials: ST
authors.lastname: Cole
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authors.lastname: Robison
authors.forename: L
authors.initials: L
authors.lastname: Richterich
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authors.lastname: Johnson
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authors.lastname: Church
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authors.lastname: Mao
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003205:Computing Methodologies; D003360:Cosmids / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000302:isolation & purification*; D016680:Genome, Bacterial; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics; D009166:Mycobacterium leprae / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D009876:Operon / Q000235:genetics; D011544:Pseudogenes; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D004269:DNA, Bacterial; D009097:Multienzyme Complexes