Molecular evolution of Mycobacterium tuberculosis.

Tuberculosis continues to be the main cause of death from a single infectious agent in developing countries. The causative agent, Mycobacterium tuberculosis, is thought to have diverged from its common ancestor as recently as 15,000 years ago. Subsequently, various genetic elements have evolved over time at different rates and can be used to elucidate patterns of infection. When individual elements are studied within genetic families, very low rates of variation are observed for almost every marker. For example, when all M. tuberculosis genetic families are considered, the number of alleles observed at each mycobacterial interspersed repetitive unit (MIRU) locus usually drops when viewed within a single genetic family, indicating that the rate of repeat variation may be low, as each member of that family is a descendant of a single common ancestor. Also, the low level of silent nucleotide variation observed indicates that M. tuberculosis is, in evolutionary terms, very young. Mapping the variation of the different markers used in molecular epidemiology within a genetic framework enables the relative rates of variation of these markers to be determined and, together with a complete chronology, allows the identification of more informative panels of markers tailored to individual genetic families.