Whole Genome Construction of Chlamydia Phylogeny

Contributed by: Tom Xia

Everyone thinks of HIV when he or she thinks of sexually transmitted infections (STIs), but at-risk college students need to be aware of Chlamydia. Caused by the bacterium Chlamydia trachomatis, Chlamydia is the most common bacterial STI (1). As of 2010, sexually transmitted Chlamydia effects 3.1% of the world’s population, and the Center of Disease Control and Prevention estimates an incidence rate of 2.8 million new cases per year in the United States, which is nearly 60 times greater than the incidence rate of HIV (2, 3). Chlamydia can be transmitted through vaginal, anal, and oral sex and can lead to diseases of the genitals and eyes (1). While the prognosis for Chlamydia is generally pretty good, a recent study has found that Chlamydia evolves differently than previously expected, which has great significance in the diagnosis and treatment of the bacterium.

Historically, the diversity of C. trachomatis was characterized by the major outer membrane protein and its gene, ompA. However, attempts to use ompA sequences to construct the C. trachomatis species phylogeny have been unsuccessful due to lack of agreement between trees produced using other gene sets (4). Harris et al. constructed a phylogeny using genome-wide single nucleotide polymorphisms (SNPs) and showed that ompA serotyping does not match the evolutionary structure of C. trachomatis because many serotypes appeared on multiple distinct branches of the tree (Fig. 1).

Figure 1. Maximum likelihood reconstruction of the species phylogeny (a) and plasmid phylogeny (b) of C. trachomatis with recombinations removed. (Harris et al (4)).

Interestingly, the whole genome analysis showed very high occurrence of homoplasic SNPs, or identical SNPs that occur independently on different branches of the phylogenetic tree (Fig. 2). Researchers found dense clusters of compatible homoplasies, which suggest that recombination was the cause of the homoplasies rather than convergent selection. This is a momentous finding as recombination events were previously thought to be very rare in C. trachomatis. In fact, recombination is most likely an ongoing process because many recombination events have occurred in recent evolutionary divergences (4).

Figure 2. Reconstruction of recombination events on the species phylogeny of C. trachomatis. (From Harris et al. (4)).

This study shows the error of using ompA serotyping to characterize different strains of Chlamydia and calls for the use of whole genome data. Current methods cannot detect subtle changes outside ompA and can potentially lead to proliferation of drug resistance. Recombination occurs frequently between different strains of Chlamydia, even those that invade different tissues, hinting at a lack of absolute barriers to the exchange of genetic data (5). Efforts must be made to improve the diagnosis of Chlamydia to include identification of different strains, and recombination events need to be thoroughly studied in anticipation of the evolution of drug resistance.

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References

1. Stamm WE, Batteiger BE (2009) Chlamydiatrachomatis (trachoma,perinatal infections, lymphogranuloma venereum, and other genital infections). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Elsevier Churchill Livingstone; chap 180.

2. Vos, T (2012) Years lived with disability (YLDs) for1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis forthe Global Burden of Disease study 2010. Lancet 380(9859):2163-96.

3. STD Trends in the United States: 2010 national Datafor Gonorrhea, Chlamydia, and Syphilis (2010) Center for Disease Control and Prevention (CDC). Retrieved Feb. 22, 2013.

4. Harris SR, Clarke IN, Seth-Smith HMB, Solomon AW, Cutcliffe LT, Marsh P, Skilton RJ, Holland MJ, Mabey D, Peeling RW, Lewis DA, Spratt BG, Unemo M, Persson K, Bjartling C, Brunham R, de Vries HJC, Morre SA, Speksnijder A, Bebear CM, Clerc M, de Barbeyrac B, Parkhill J, Thomson NR (2012) Whole genomeanalysis of diverse Chlamydia trachomatis strains identifies phylogeneticrelationships masked by current clinical typing. Nat Genet 44(4):413-S1.

5. STD tracing shows Chlamydia evolved more actively than thought (2012) Redorbit. Retrieved Feb. 22, 2013.