Negligible genetic diversity of Mycobacterium tuberculosis host immune system protein targets: Evidence of limited selective pressure

A common theme in medical microbiology is that the amount of amino acid seq uence variation in proteins that are targets of the host immune system grea tly exceeds that found in metabolic enzymes or other housekeeping proteins. Twenty-four Mycobacterium tuberculosis genes coding for targets of the hos t immune system were sequenced in 16 strains representing the breadth of ge nomic diversity in the species. Of the 24 genes, 19 were invariant and only six polymorphic nucleotide sires were identified in the 5 genes that did h ave variation. The results document the highly unusual circumstance that pr ominent M. tuberculosis antigenic proteins have negligible structural varia tion worldwide. The data are best explained by a combination of three facto rs: (i) evolutionarily recent global dissemination in humans, (ii) lengthy intracellular quiescence, and (iii) active replication in relatively few fu lly immunocompetent hosts. The very low level of amino acid diversity in an tigenic proteins may be cause for optimism in the difficult fight to contro l global tuberculosis.