Comparing genomes within the species Mycobacterium tuberculosis

The study of genetic variability within natural populations of pathogens ma y provide insight into their evolution and pathogenesis. We used a Mycobact erium tuberculosis high-density oligonucleotide microarray to detect small- scale genomic deletions among 19 clinically and epidemiologically well-char acterized isolates of M. tuberculosis. The pattern of deletions detected wa s identical within mycobacterial clones but differed between different clon es, suggesting that this is a suitable genotyping system for epidemiologic studies. An analysis of genomic deletions among an extant population of pat hogenic bacteria provided a novel perspective on genomic organization and e volution. Deletions are likely to contain ancestral genes whose functions a re no longer essential for the organism's survival, whereas genes that are never deleted constitute the minimal mycobacterial genome. As the amount of genomic deletion increased, the likelihood that the bacteria will cause pu lmonary cavitation decreased, suggesting that the accumulation of mutations tends to diminish their pathogenicity. Array-based comparative genomics is a promising approach to exploring molecular epidemiology, microbial evolut ion, and pathogenesis.