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Envelope proteins

Intraserovar recombination in MOMP.

The previous section showed how the serovar specificity of C. trachomatis is largely determined by surface exposed epitopes on the surface exposed variable sequences, particularly VS 1, 2 and 4. There was therefore considerable interest to explain why some rare isolates of C. trachomatis could not be typed. The sequence of the ompA of such variants was therefore determined. Thus serovar  Ia was a combination of serovars I and H [Lampe et al., 1993]; 4 to 8% of STD strains were combinations of serovars C and J and I and H  [Manitoba: Yang et al., 1993] or of serovars L1/L2, L2/L1, L3/H, or I/H  [Kenyan prostitutes: Brunham et al., 1994] while perhaps clearest of all, three 'untypable' LGV strains from South African (strains LGV-98, LGV-224, and LGV-115) were composed  almost equally of sequence derived from LGV serovars L1 and L2 with a clear cross-over point in VS2  [Hayes et al., 1994]. Others however reported  no apparent recombinants among the ompA sequences of: 68 STD strains in San Francisco [Dean et al., 1995]; 188 trachoma strains in the Gambia [Hayes et al., 1995]  or among 27 trachoma strains in Tunisia [Dean et al., 1992]. 

Fig 1

A computational search for evidence for recombination in  24 ompA and 10 omcB sequences found that phylogenetic reconstructions were not congruent for the C. trachomatis strains. The genetic distance between serovars L1 and B was ten times greater for MOMP than for OmcB, even though  the average genetic distance between species was only 25% greater for MOMP than for OmcB. They suggested the most plausible explanation was that of genetic exchange among strains due to recombination events [Fitch, Peterson, and de la Maza, 1993]. Recombination events probably also occur in other Chlamydiaceae membrane proteins, although theyhave been little studied. In C. pneumoniae, Jordan et al., 2000 identified one apparent gene conversion event between two genes that encoded putative outer membrane proteins of C. pneumoniae strain AR39.

Millman et al., 2001 employed statistical methods [Sawyer runs test, compatability matrices and index of association analyses] to search for evidence of intragenic recombination or linkage equilibrium, comparing sequences of the major outer membrane protein (MOMP) gene (ompA) and the outer membrane complex B protein gene (omcB) from C. trachomatis, C. pneumoniae and C. psittaci.  were analyzed for evidence of intragenic recombination and for linkage equilibrium. Substantial evidence was found that there has been a history of intragenic recombination at ompA, including one instance of interspecies recombination between C. muridarium and the equine C. pneumoniae strain N16. No intragenic recombination was detected within omcB, although differences in divergence suggested that there has been intergenic recombination involving the omcB gene. For C. trachomatis ompA gene, a higher degree of recombination was found for C rather than B subclass strains [See: MOMP and serology] and recombination was highest in the downstream half of the gene. Many significant breakpoints were found in VS 3 and 4 of MOMP for the recombinant strains D/B120, G/UW-57, E/Bour, and LGV-98 identified in this study. To explain the discordant phylogenies between ompA and omcB it is clear there must be a major breakpoint between these two genes. Either only ompA is involved in recombination or the whole of omcB is involved in recombination. Differences in selection pressure from the immune system probably explain the observed differences between these two genes. It is suggested that human C. trachomatis strains evolved more quickly for omcB than for ompA or for other Chlamydiaceae.  The reader is referred to the excellent discussion in the paper of Millman et al., 2001 for further thoughts on the evolution of these genes and their possible role in immune evasion.

[MEW] April 2002

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References

Brunham, R., Yang, C., Maclean, I., Kimani, J., Maitha, G. and Plummer, F. 1994. Chlamydia trachomatis from individuals in a sexually transmitted disease core group exhibit frequent sequence variation in the major outer membrane protein (ompA) gene. Journal of Clinical Investigation 94, 458 - 463 [RFLP and sequencing study in high risk Kenyan prostitutes. Substantial polymorphisms]

Dean, D., Oudens, E. M., Padian, N., Bolan, G. and Schachter, J. (1995). Major outer membrane protein variants of Chlamydia trachomatis are associated with severe upper genital tract infections and histopathology in San Francisco. Journal of Infectious Diseases 172, 1013 - 1022. [Suggests serovar F is more likely to cause pelvic inflammatory disease but statistically, numbers are low] 

Dean, D., Schachter, J., Dawson, C. and Stephens, R. S. (1992). Comparison of the major outer membrane protein sequence variant regions of B/Ba isolates: a molecular epidemiologic approach to Chlamydia trachomatis infections. Journal of  Infectious Diseases 166, 383 - 392. [Small study]

Fitch, W. M., Peterson, E. M. and de la Maza, L. M. (1993). Phylogenetic analysis of the outer-membrane-protein genes of Chlamydiae, and its implication for vaccine development. Molecular Biology and Evolution 10, 892 - 913. Full article

Hayes, L. J., Yearsley, P., Treharne, J. D., Ballard, R., Fehler, G. H. & Ward, M. E. (1994). Evidence for naturally occurring recombination in the gene encoding the major outer membrane protein of lymphogranuloma venereum isolates of C. trachomatis. Infection and  Immunity 62, 5659 - 5663. [Clear cross over point in VS2 subsequently confirmed by Millman et al., 2001]

Hayes, L. J., Pecharatana, S., Bailey, R. L., Hampton, T. J., Pickett, M. A., Mabey, D. C., Watt, P. J. and Ward, M. E. (1995). Extent and kinetics of genetic change in the ompl gene of Chlamydia trachomatis in two villages with endemic trachoma. Journal of Infectious Diseases 172, 268 - 272 [Whole Gambian villages ompA sequencing study; relatively few ompA polymorphisms]

Jordan, I. K., Makarova, K. S., Wolf, Y. I. and Koonin, E. V. (2000). Gene conversions in genes encoding outer-membrane proteins in H. pylori and C. pneumoniae. Trends in Genetics 17, 7 - 10. 

Lampe, M. F., Suchland, R. J. and Stamm, W. E. (1993). Nucleotide sequence of the variable domains within the major outer membrane protein gene from serovariants of Chlamydia trachomatis. Infection and Immunity 61, 213 - 219

Millman, K. L., Tavare, S. & Dean, D. (2001). Recombination in the ompA gene but not the omcB gene of Chlamydia contributes to serovar-specific differences in tissue tropism, immune surveillance, and persistence of the organism. Journal of Bacteriology 183, 5997 - 6008. Full article [Excellent and thoughtful study. Good literature review].

Yang, C. L., Maclean, I. & Brunham, R. C. (1993). DNA sequence polymorphism of the Chlamydia trachomatis ompA gene. Journal of  Infectious Diseases 168, 1225 - 1230

NEXT: T cell epitopes on MOMP