Negligible Genetic Diversity of Mycobacterium Tuberculosis Host Immune System Protein Targets: Evidence of Limited Selective Pressure

Genetics. 2000 May;155(1):7-16.


A common theme in medical microbiology is that the amount of amino acid sequence variation in proteins that are targets of the host immune system greatly exceeds that found in metabolic enzymes or other housekeeping proteins. Twenty-four Mycobacterium tuberculosis genes coding for targets of the host immune system were sequenced in 16 strains representing the breadth of genomic diversity in the species. Of the 24 genes, 19 were invariant and only six polymorphic nucleotide sites were identified in the 5 genes that did have variation. The results document the highly unusual circumstance that prominent M. tuberculosis antigenic proteins have negligible structural variation worldwide. The data are best explained by a combination of three factors: (i) evolutionarily recent global dissemination in humans, (ii) lengthy intracellular quiescence, and (iii) active replication in relatively few fully immunocompetent hosts. The very low level of amino acid diversity in antigenic proteins may be cause for optimism in the difficult fight to control global tuberculosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyltransferases*
  • Amino Acid Sequence
  • Antigens, Bacterial / genetics*
  • Bacterial Proteins / genetics
  • Genetic Variation*
  • Glycoproteins / genetics
  • Humans
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / genetics*
  • Sequence Homology, Amino Acid
  • Tuberculosis / immunology
  • Tuberculosis / microbiology


  • 19 kDa antigen, Mycobacterium
  • 45-47 kDa antigen complex, Mycobacterium
  • Antigens, Bacterial
  • Bacterial Proteins
  • Glycoproteins
  • MPB64 protein, Mycobacterium
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis
  • antigen 85C, Mycobacterium tuberculosis