MULTIPLEX SEQUENCING OF 1.5 MB OF THE MYCOBACTERIUM-LEPRAE GENOME

The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium le prae was determined using computer-assisted multiplex sequencing techn ology. This brings the 2.8-Mb M. leprae genome sequence to similar to 66% completion. The sequences, derived from 43 recombinant cosmids, co ntain 1046 putative protein-coding genes, 44 repetitive regions, 3 rRN As, 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% ha ve significant matches to genes with well-defined functions. Compariso n 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 virule nce proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) opero ns, inteins, and highly fragmented pseudogenes.