Phylogenetic analysis of Chlamydia trachomatis.

Abstract

An understanding of the evolution and biological relationships of Chlamydia trachomatis major outer membrane protein (MOMP) and MOMP gene (omp1) sequences is an ongoing process and one that requires complex analyses. In our estimation, the study by Stothard et al. (5) is limited by the lack of sufficient numbers of omp1 genotypes for the analysis presented and by the use of only one method for evaluation of the molecular evolution of chlamydiae. For example, the authors state that what causes lymphogranuloma venereum, trachoma, or urogenital strains to infect certain cell types cannot be explained by MOMP. This conclusion is based solely on phylogenetic reconstructions of 6 trachoma and 22 nontrachoma genotypes. For MOMP, phylogenetic analyses may be more difficult to interpret since diversity is probably generated by means other than simple substitutions and insertions and deletions (indels); current tree topologies may be obscured by recombination events such that a common ancestor for genotypes with similar disease presentations can no longer be identified. We believe that estimates of mutation rates and other more complicated analyses are needed before any firm conclusions can be made. Further, the collection of published sequences does not necessarily represent the extent of omp1 diversity and may not be adequate to describe molecular evolution for chlamydiae. For example, fewer omp1 variants have been described for E than for D and F. As more genotyping has been performed, additional E variants have been identified: Stothard et al. report 3 variants of 19 (16%); we previously found 11 variants of 67 (16%) (2). Thus, additional sequencing of omp1 from multiple trachoma and sexually transmitted disease specimens worldwide is needed to determine a representative distribution of all genotypes for analysis. The authors correctly mention that our E/Bour sequence is different from that of Peterson et al. (4). They state that “variation in E/Bour reported by Dean and Millman is not easily explained.” Herein, we provide an explanation. E/Bour was first described in the 1950s when serotyping was the only method for identifying chlamydial subtypes. The sequence differences between that of Peterson et al. and ours reside in conserved regions of omp1; variable segments of our sequence are exactly the same as that published by Yuan et al. (6). Since serotyping is based on antibody reactivity to variable segments of MOMP, it is highly probable that different clones of serovar E were labeled similarly as E/Bour. The source of E/Bour may also differ; ours was from Dr. Julius Schachter, San Francisco, Calif. Further, although the authors found no evidence for “culture-induced … mutation,” this is an in vitro system that does not necessarily reflect the selective pressure of an in vivo environment. In fact, there is in vivo evidence for allelic flux. Hayes et al. (3) observed flux in The Gambia, albeit with minimal nonsynonymous mutations over 18 months. Dean et al. (1) found significant flux over 3 years in Tunisia. Thus, some mutational drift may have occurred in vivo before E clones were serotyped and labeled as E/Bour in the 1950s.