The Decaying Genome of Mycobacterium leprae

Leprosy, one of the most feared diseases of history, was well known in ancient times and is still a major public health problem today; from 2 million to 3 million people are affected worldwide, and approximately 650,000 new cases are reported each year. In its severest form, leprosy causes paralysis, blindness, and disfigurement. Although human genes play some role in susceptibility to leprosy, the disease is caused by the bacterium Mycobacterium leprae, which infects cells of the nervous system and causes nerve damage, sensory loss, and disfigurement. In 1873, Armauer Hansen observed these bacteria in tissue samples taken from people with leprosy, but to this day no one has successfully cultured the bacterium in laboratory media, severely restricting the study of the disease agent.

In 2001, scientists in Britain and France determined the sequence of the entire genome of M. leprae. Comparing its genome with that of its close relative M. tuberculosis (the pathogen that causes tuberculosis) and other mycobacteria has been a source of important insight into the unique properties of this pathogen.

The genome of M. leprae is 3,268,203 bp in size, 1 million base pairs smaller than the genomes of other mycobac-teria. In most bacterial genomes, the vast majority of the DNA encodes proteins—there is little noncoding DNA between genes. In contrast, only 50% of the DNA of M. leprae encodes proteins (Table 19.1), and M. leprae has 2300 fewer genes than M. tuberculosis. An incredible 27% of M. leprae's genome consists of pseudogenes—nonfunc-tional copies of genes that have been inactivated by mutations. M. leprae has 1116 pseudogenes, whereas its close relative, M. tuberculosis, has just 6.

Comparison of the genomes of Mycobacterium leprae, which causes leprosy, and Mycobacterium tuberculosis, which causes tuberculosis

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