Mycobacterium Leprae Genome
Mycobacterium leprae has the longest doubling time of all known bacteria, and has thwarted every effort at culture in the laboratory. Comparing the genome sequence of M. leprae with that of Mycobacterium tuberculosis provides clear explanations for these properties, and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes. Gene deletion and decay appear to 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.
The genome sequence of a strain of M. leprae, originally isolated in Tamil Nadu and designated TN, has been completed recently. The sequence was obtained by a combined approach, employing automated DNA sequence analysis of selected cosmids and whole-genome 'shotgun' clones. After the finishing process, the genome sequence was found to contain 3,268,203 base pairs (bp), and to have an average G+C content of 57.8%, values much lower than the corresponding values for M. tuberculosis, which are 4, 441,529 bp and 65.6% G+C,. About 1500 genes are common to both M. leprae and M. tuberculosis. The comparative analysis suggests both mycobacteria derived from a common ancestor and, at one stage, had gene pools of similar size. Downsizing from a genome of 4.42 Mbp, such as that of M. tuberculosis, to one of 3.27 Mbp would account for the loss of some 1200 protein-coding sequences. There is evidence that many of the genes that were present in the genome of the common ancestor of M. leprae and M. tuberculosis have been lost by recombination in the M.leprae genome.
Information from the completed genome can be useful to develop diagnostic skin tests, to understand the mechanisms of nerve damage and drug resistance and to identify novel drug targets for rational design of new therapeutic regimens and drugs to treat leprosy and its complications.
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