Interplay of recombination and selection in the genomes of Chlamydia trachomatis

Abstract

BackgroundChlamydia trachomatis is an obligate intracellular bacterial parasite, which causes several severe and debilitating diseases in humans. This study uses comparative genomic analyses of 12 complete published C. trachomatis genomes to assess the contribution of recombination and selection in this pathogen and to understand the major evolutionary forces acting on the genome of this bacterium.ResultsThe conserved core genes of C. trachomatis are a large proportion of the pan-genome: we identified 836 core genes in C. trachomatis out of a range of 874-927 total genes in each genome. The ratio of recombination events compared to mutation (ρ/θ) was 0.07 based on ancestral reconstructions using the ClonalFrame tool, but recombination had a significant effect on genetic diversification (r/m = 0.71). The distance-dependent decay of linkage disequilibrium also indicated that C. trachomatis populations behaved intermediately between sexual and clonal extremes. Fifty-five genes were identified as having a history of recombination and 92 were under positive selection based on statistical tests. Twenty-three genes showed evidence of being under both positive selection and recombination, which included genes with a known role in virulence and pathogencity (e.g., ompA, pmps, tarp). Analysis of inter-clade recombination flux indicated non-uniform currents of recombination between clades, which suggests the possibility of spatial population structure in C. trachomatis infections.ConclusionsC. trachomatis is the archetype of a bacterial species where recombination is relatively frequent yet gene gains by horizontal gene transfer (HGT) and losses (by deletion) are rare. Gene conversion occurs at sites across the whole C. trachomatis genome but may be more often fixed in genes that are under diversifying selection. Furthermore, genome sequencing will reveal patterns of serotype specific gene exchange and selection that will generate important research questions for understanding C. trachomatis pathogenesis.ReviewersThis article was reviewed by Dr. Jeremy Selengut, Dr. Lee S. Katz (nominated by Dr. I. King Jordan) and Dr. Arcady Mushegian.

Emancipating Chlamydia: Advances in the Genetic Manipulation of a Recalcitrant Intracellular Pathogen

“…Comparative genomic analyses of more than 65 clinical strains have provided evidence that LGT events within and between C. trachomatis biovars are natural and common occurrences (4,13,(126)(127)(128). Such analyses also indicated that genetic exchange is more likely between strains with tropism for the same site of infection (4,(126)(127)(128).…”

“…Such analyses also indicated that genetic exchange is more likely between strains with tropism for the same site of infection (4,(126)(127)(128). However, there are now multiple examples of interbiovar DNA exchange (4,122,127) in which strains with tropisms for different infection sites exchange DNA, suggesting that there are no absolute barriers to genetic exchange.…”

Polymorphisms in Inc Proteins and Differential Expression ofincGenes among Chlamydia trachomatis Strains Correlate with Invasiveness and Tropism of Lymphogranuloma Venereum Isolates

“…In addition, almost all disease group-specific amino acids of Inc proteins encoded by genes likely under positive selection were found among proteins of LGV strains, and the majority of these amino acids localized in regions of the proteins predicted to face the host cell cytosol (Table 2). However, it must be clarified that other proteins in addition to Inc proteins are likely involved in the specificity of infection by LGV strains (8,30). Moreover, the overall determinants of tissue tropism of C. trachomatis should be complex and multifactorial and should certainly also include, e.g., the products of the trpRBA operon (10,19,51) or of the cytotoxin gene (11) and Tarp (34).…”

“…These experiments were essentially done as previously described (7,42). Briefly, for each strain, six tissue culture flasks with a surface area of 25 cm 2 containing monolayers of HeLa 229 cells were inoculated at a multiplicity of infection of 1; cells were harvested at 2,6,12,20,30, and 42 h postinfection by scraping in ice-cold phosphate-buffered saline. The cell suspension was sonicated to disrupt mammalian cells and promote bacterial release, followed by low-speed centrifugation at 4°C.…”

Culture-independent sequence analysis of Chlamydia trachomatis in urogenital specimens identifies regions of recombination and in-patient sequence mutations

“…Studying these genetically difficult organisms has become less arduous, with the recent advent of high-throughput sequencing technologies and workable genetic systems (Wang et al, 2011). While acquisition by chlamydiae of genetic material from other species is considered rare (Dugan et al, 2004), recombination within C. trachomatis, both in vitro and in vivo, appears to be relatively common (Dugan et al, 2004;Gomes et al, 2004Gomes et al, , 2007Harris et al, 2012;Jeffrey et al, 2010;Joseph et al, 2011;Somboonna et al, 2011;Srinivasan et al, 2012). Recombination has been documented between the lymphogranuloma venereum and urogenital biovars, fusogenic and non-fusogenic strains (Jeffrey et al, 2013), and strains with tropism for different tissues (Harris et al, 2012;Jeffrey et al, 2010).…”