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Journal of Bacteriology, April 2004, p. 2457-2465, Vol. 186, No. 8
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.8.2457-2465.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Population-Based Genetic and Evolutionary Analysis of Chlamydia trachomatis Urogenital Strain Variation in the United States{dagger}

Kim Millman,1,2 Carolyn M. Black,3 Robert E. Johnson,3 Walter E. Stamm,4 Robert B. Jones,5 Edward W. Hook,6 David H. Martin,7 Gail Bolan,8 Simon Tavaré,1,9 and Deborah Dean2,10*

Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California 90033,1 Centers for Disease Control and Prevention, Atlanta, Georgia 30333,3 Division of Infectious Diseases, University of Washington Medical Center, Seattle, Washington 98195,4 Wishard Health Services, Indianapolis, Indiana 46202,5 Division of Infectious Diseases, University of Alabama, Birmingham, Birmingham, Alabama 35294,6 Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112,7 Sexually Transmitted Disease Control, California Department of Health Services, Berkeley, California 94704,8 Departments of Biological Sciences and Mathematics, University of Southern California, Los Angeles, California 90089,9 Children's Hospital Oakland Research Institute (CHORI), Oakland, California 94609,2 Department of Medicine, University of California at San Francisco School of Medicine, San Francisco, California 94143,10

Received 5 September 2003/ Accepted 19 December 2003

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.

* Corresponding author. Mailing address: Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609. Phone: (510) 450-7655. Fax: (510) 450-7910. E-mail: ddean{at}chori.org.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

Journal of Bacteriology, April 2004, p. 2457-2465, Vol. 186, No. 8
0021-9193/04/$08.00+0     DOI: 10.1128/JB.186.8.2457-2465.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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