Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 Rue du Dr Roux, 75724 Paris Cedex 15, France and *The Sanger Centre, Wellcome Trust Genome Campus, Hinxton CB10 1IL, UK
Abstract. The powerful combination of genomics and bioinformatics is providing a wealth of information about Mycobacterium tuberculosis, the aetiological agent of human tuberculosis, that will facilitate the conception and development of new therapies. The starting point for genome sequencing was the integrated map of the 4.4 Mb circular chromosome of the widely used, virulent reference strain, M. tuberculosis H37Rv. Cosmids and bacterial artificial chromosomes were selected from ordered libraries and subjected to systematic shotgun sequence analysis. This approach simplified sequence assembly as the genome is rich in repetitive DNA. In common with most bacteria, > 90% of the potential coding capacity is used, and probable or tentative functions could be attributed to > 70% of the genes. The potential biological roles of two of the principal driving forces in genome dynamics, insertion sequence elements and polymorphic multigene families are discussed.
1998 Genetics and tuberculosis. Wiley, Chichester (Novartis Foundation Symposium 217) p 160-177
One of the most significant and far-reaching events in the history of molecular biology was undoubtedly the deciphering of the genetic code in the 1960s, and the subsequent demonstration of its ubiquitous use by all forms of life, ranging from relatively simple micro-organisms such as bacteria to complex mammals like humans. This ability to read the message encoded in the genes enabled the predictions of the 'central dogma', the flow of information from DNA, via RNA to proteins, to be tested experimentally. Thanks to striking technological developments in the fields of DNA sequencing and bioinformatics, it is now a relatively straightforward task to obtain the sequences of large numbers of genes rapidly or, in the case of a bacterium like Mycobacterium tuberculosis, to sequence the whole genome. The enormous progress made in computer-assisted database searching during the last few years, coupled with the ability to perform reverse genetics, means that the functions of the majority of the genes can now be predicted in silico then tested in the laboratory.
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