Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing

Abstract

Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.

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Figure 1: Maximum likelihood reconstruction of the phylogeny of C. trachomatis with recombinations removed.
Figure 2: Reconstruction of recombination events on the species phylogeny of C. trachomatis.
Figure 3: Distribution of SNPs in ompA of C. trachomatis.

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NCBI Reference Sequence

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Acknowledgements

We thank the core informatics, library-making and sequencing teams at the Wellcome Trust Sanger Institute. S.R.H. is grateful for the opportunity to discuss this project at the Permafrost conference. This work was funded by the Wellcome Trust grant numbers 098051 and 080348. B.G.S. was funded by the Wellcome Trust.

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S.R.H. assembled, aligned and analyzed the data and wrote the paper. I.N.C. jointly conceived of the project with N.R.T. and provided samples. H.M.B.S.-S. performed experiments, carried out analyses of the data and helped write the paper. L.T.C., P.M., R.J.S., M.J.H., D.M., R.W.P., D.A.L., M.U., K.P., C.B., R.B., H.J.C.d.V., S.A.M., A.W.S., C.M.B., A.S., M.C. and B.d.B. collected and cultured samples. B.G.S. and J.P. helped interpret the data and write the paper. N.R.T. conceived of and ran the project and wrote the paper.

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Correspondence to Simon R Harris.

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Harris, S., Clarke, I., Seth-Smith, H. et al. Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing. Nat Genet 44, 413–419 (2012). https://doi.org/10.1038/ng.2214

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