title: Population-based genetic and evolutionary analysis of Chlamydia trachomatis urogenital strain variation in the United States.
abstract: Chlamydia trachomatis is a major cause of ocular and sexually transmitted diseases worldwide. While much of our knowledge about its genetic diversity comes from serotyping or ompA genotyping, no quantitative assessment of genetic diversity within serotypes has been performed. To accomplish this, 507 urogenital samples from a multicenter U.S. study were analyzed by phylogenetic and statistical modeling. No B, Da, or I serotypes were represented. Based on our analyses, all but one previous urogenital B serotype was identified as Ba. This, coupled with the lack of B serotypes in our population, suggests that B has specific tropism for ocular mucosa. We identified a Ba/D recombinant (putative crossover nucleotide 477; P < 0.0001) similar to a B/D mosaic we described previously from an African trachoma patient. Computational analyses of the Ba/D recombinant indicated that upstream changes were less important for tissue tropism than downstream incorporation of the D sequence. Since most serotypes had nonsynonymous/synonymous ratios of <1.0, the major outer membrane protein, encoded by ompA, has many functional constraints and is under purifying selection. Surprisingly, all serotype groups except for J had a unimodal population structure indicating rapid clonal expansion. Of the groups with a unimodal structure, E and Ia and, to a lesser extent, G and K were prevalent, had infrequent incorporation of mutations, and, compared to other groups, had a relatively greater degree of diversifying selection, consistent with a selective sweep of mutations within these groups. Collectively, these data suggest a diverse evolutionary strategy for different serogroups of the organism.
authors.affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Millman
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Black
authors.forename: Robert E
authors.initials: RE
authors.lastname: Johnson
authors.forename: Walter E
authors.initials: WE
authors.lastname: Stamm
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jones
authors.forename: Edward W
authors.initials: EW
authors.lastname: Hook
authors.forename: David H
authors.initials: DH
authors.lastname: Martin
authors.forename: Gail
authors.initials: G
authors.lastname: Bolan
authors.forename: Simon
authors.initials: S
authors.lastname: Tavaré
authors.forename: Deborah
authors.initials: D
authors.lastname: Dean
mesh_terms: D000293:Adolescent; D000328:Adult; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D005075:Biological Evolution; D002690:Chlamydia Infections / Q000453:epidemiology / Q000382:microbiology*; D002692:Chlamydia trachomatis / Q000737:chemistry / Q000145:classification / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D052801:Male Urogenital Diseases / Q000453:epidemiology / Q000382:microbiology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D012703:Serotyping; D014481:United States / Q000453:epidemiology; D014505:Urban Population
chemical_list: D001425:Bacterial Outer Membrane Proteins; C078167:OMPA outer membrane proteins