Phylogenetic analysis of the outer-membrane-protein genes of Chlamydiae, and its implication for vaccine development

Examination of 18 complete and 6 partial sequences of the major outer-membrane protein from 24 chlamydiae isolates was used to reconstruct theirevolutionary relationships. From this analysis, assuming that the cladeswith 100% bootstrap support are correct, come the following conclusions:(1) The tree of these sequences is not congruent with the phylogeny of thehosts, and thus host switching would seem to have occurred, therebylimiting the extent to which there has been coevolution of parasite andhost. (2) The tree is also noncongruent with clustering by type of cellinfected, thereby limiting the extent to which there has been coevolutionof parasite and the cell type that it infects. (3) The tree is alsononcongruent with clustering by the organ infected (eyes or genitalia),thereby limiting the extent to which there has been coevolution of parasiteand the organ that it infects. (4) The tree is also noncongruent withgenital strains arising from lymphogranuloma venereum strains. (5) The treeis also noncongruent with the geographic site at which the isolates wereobtained, thereby limiting the extent of divergence explained by geographicseparation. (6) There are estimated to be 185 amino acid positions that areinvariable (as opposed to unvaried) in the major outer-membrane protein.There are 10 unvaried positions in the variable domains, of which 9 appearto be invariable, giving some reason to hope that development of a vaccinemight be possible. (7) The rate of change of this protein is too small tosee increased divergence over the time span of isolation of these genes,giving hope to any vaccine having longevity. Bootstrapping supports thoseportions of the tree on which the first five conclusions above depend. Thepicture that these results provide is more one of pathogen versatility thanone of coevolutionary constraints. In addition, we examined 10 60-KDa,outer-membrane protein- 2 genes, all but one of which were from these samestrains. The tree was not, among the trachomatis strains, congruent withthe major-outer- membrane protein tree, suggesting that gene exchange couldbe occurring among strains. Moreover, there is an apparent slowdown indivergence in this gene, among the trachomatis strains.