Mycobacterium tuberculosis, the scourge of humanity, is one of the most successful and scientifically challenging pathogens of all time. To catalyse the conception of new prophylactic and therapeutic interventions against tuberculosis, and to enhance our understanding of the biology of the tubercle bacillus, the complete genome sequence of the most widely used strain, H37Rv, has been determined. Bioinformatic analysis led to the identification of ~4000 genes in the 4.41 Mb genome sequence and provided fresh insight into the biochemistry, physiology, genetics and immunology of this much-feared bacterium. Genomic information is centralised in TubercuList (http://www.pasteur.fr/Bio/TubercuList/).

Original genome annotations need to be regularly updated if the information they contain is to remain accurate and relevant. Here the complete re-annotation of the genome sequence of Mycobacterium tuberculosis strain H37Rv is presented almost 4 years after the first submission. Eighty-two new protein-coding sequences (CDS) have been included and 22 of these have a predicted function. The majority were identified by manual or automated re-analysis of the genome and most of them were shorter than the 100 codon cut-off used in the initial genome analysis. The functional classification of 643 CDS has been changed based principally on recent sequence comparisons and new experimental data from the literature. More than 300 gene names and over 1000 targeted citations have been added and the lengths of 60 genes have been modified. Presently, it is possible to assign a function to 2058 proteins (52% of the 3995 proteins predicted) and only 376 putative proteins share no homology with known proteins and thus could be unique to M. tuberculosis.

Genomics is providing us with a mass of information about the biochemistry, physiology and pathogenesis of Mycobacterium tuberculosis and Mycobacterium leprae. Comparison of the two genome sequences is mutually enriching and indicates that the M. leprae genome appears to have undergone shrinkage and large-scale gene inactivation, which may account for the exceptionally slow growth of this organism.