Directional Evolution of Chlamydia trachomatis towards Niche-Specific Adaptation

Abstract

On behalf of the host-pathogen "arms race," a cutting-edge approach for elucidating genotype-phenotype relationships relies on the identification of positively selected loci involved in pathoadaptation. We studied the obligate intracellular bacterium Chlamydia trachomatis, for which same-species strains display a nearly identical core and pan genome, while presenting a wide range of tissue tropism and ecological success. We sought to evaluate the evolutionary patterns underlying species separation (divergence) and C. trachomatis serovar radiation (polymorphism) and to establish genotype-phenotype associations. By analyzing 60 Chlamydia strains, we detected traces of Muller's ratchet as a result of speciation and identified positively selected genes and codons hypothetically involved in the infection of different human cell types (e.g., columnar epithelial cells of ocular or genital mucosae and mononuclear phagocytes) and also events likely driving pathogenic and ecological success dissimilarities. In general, these genes code for proteins involved in immune response elicitation, proteolysis, and the subversion of host-cell functions, and also for proteins with unknown function(s). Several genes are potentially involved in more than one adaptive process, suggesting multiple functions or a distinct modus operandi for a specific function, and thus should be considered as crucial research targets. In addition, six of the nine genes encoding the putative antigen/adhesin polymorphic membrane proteins seem to be under positive selection along specific serovars, which sustains an essential biological role of this extra-large paralogue family in chlamydial pathobiology. This study provides insight into how evolutionary inferences illuminate ecological processes such as adaptation to different niches, pathogenicity, or ecological success driven by arms races. G enomic changes of microbial pathogens are directly linked to the evolutionary "arms race" that takes place between microbe and host during the infectious process, as a result of the antagonistic interaction, and they are a consequence of polymorphisms accumulated after selective pressure from the host's inflammatory or immune response (32). However, the majority of coding genes present a higher number of synonymous rather than nonsynonymous substitutions, which indicates that purifying selection is operating to preserve the current function and structure of the protein, and only a small fraction of the genes are expected to be positively selected where diversification is favored through increased fitness (11). In order to understand the evolutionary forces that act on gene variation, major challenges are to identify loci that might have been under selection and to determine the type of natural selection that has influenced their evolutionary history (59). In the field of infectious diseases, site-specific inferences regarding positive selection on loci involved in drug resistance (19) or in the interaction with the host immune system have been proposed as complemen...

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

“…We reveal that the overall degree of variation in the amino acid sequences of Inc proteins among strains is similar to that of a characteristic family of C. trachomatis polymorphic proteins (Pmps). Our results strengthen previous studies that suggested that some C. trachomatis Inc proteins could contribute to tissue tropism (8,9,35,43) and confirm recent data suggesting that many inc genes could be under positive selection (8,30). However, almost all of these previous studies analyzed a limited number of sequences, as the majority of the 51 genomic sequences used in our work became available only very recently (25).…”

“…3). Moreover, polymorphisms in C. trachomatis genomes are essentially driven by fixation of silent mutations (8). This suggests that the amino acid differences between Inc proteins should not be explained solely by genetic drift.…”

“…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).…”

Global Multilocus Sequence Type Analysis of Chlamydia trachomatis Strains from 16 Countries

“…Previous ompA typing studies have shown that specific genotypes are frequently found in rectal samples from MSM (39)(40)(41)(42), and tissue tropism has been suggested as an explanation (35,(43)(44)(45)(46), mainly based on genetic and cell biological findings. However, recent MLST data show that differing sexual network structures and distributions of C. trachomatis strains in MSM versus heterosexual networks may be an important reason for the findings of certain genotypes in rectum (21).…”

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

“…There is also evidence of positively selected genotypes that align with tissue tropism (ocular, genital, mononuclear/ invasive). For example, in a review of 59 C. trachomatis genome sequences, it was reported that the Tarp gene and the pmp genes have positively selected polymorphisms that cluster significantly with tissue niches (41). Polymorphisms in three distinct open reading frames have been found to associate with rectal but not cervical serovar G isolates, and two further open reading frame polymorphisms were found to associate with rectal and cervical tropism of serovars E, F, and J (42).…”