MBE Advance Access published online on June 8, 2005
Molecular Biology and Evolution, doi:10.1093/molbev/msi184
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1 Department of Integrative Biology, Brigham Young University, Provo UT 84602, USA
* To whom correspondence should be addressed. Baltimore, MD, is an urban community with a high prevalence of Neisseria gonorrhoeae. Due to partially protective immune responses, introduction of new strains from other host populations, and exposure of N. gonorrhoeae to antibiotics, the phenotypic and genotypic characteristics of the circulating strains can fluctuate over time. Understanding the overall genetic diversity and population structure of N. gonorrhoeae is essential for informing public health interventions to eliminate this pathogen. We studied gonococci population genetics in Baltimore by analyzing a hyper-variable and strongly selected outer membrane porB gene and thirteen slowly-evolving and presumably neutral housekeeping genes (abcZ, adk, aroE, fumC, gdh, glnA, gnd, pdhC, pgm, pilA, ppk, pyrD, and serC) in 204 isolates collected in 1991, 1996, and 2001 from male and female patients of two public sexually transmitted diseases clinics. Genetic diversity (
Accepted May 24, 2005
Research Article
Population Genetics of Neisseria gonorrhoeae in a High Prevalence Community Using a Hyper-Variable Outer Membrane porB and Thirteen Slowly-Evolving Housekeeping Genes
2 Department of Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, MD 21287
3 Division of Infectious Diseases, Johns Hopkins University, School of Medicine, Baltimore, MD 21287
4 Department of Integrative Biology, Brigham Young University, Provo UT 84602, USA; Department of Microbiology and Molecular Biology, Brigham Young University, Provo UT 84602, USA
Keith A. Crandall, E-mail: keith_crandall{at}byu.edu
Abstract 
), recombination (C), growth (g), population structure, and adaptive selection under codon-substitution and amino acid property models were estimated and compared between these two gene classes. Estimates of the FST fixation index and the 
2 test of sequence absolute frequencies revealed significant temporal substructuring for both gene types. Baltimore's N. gonorrhoeae populations have increased since 1991 as indicated by consistent positive values of g. Female patients showed similar or lower levels of and C than male patients. Within the MLST housekeeping genes, levels of and C ranged from 0.001 - 0.013 and 0.000 - 0.018, respectively. Overall recombination seems to be the dominant force driving evolution in these populations. All loci showed amino acid sites and physicochemical properties under adaptive (or positive-destabilizing) selection, rejecting the generally assumed hypothesis of stabilizing selection for these MLST genes. Within the porB gene, PIB showed higher and C values than PIA, however both mutation and recombination seem to play a role in their evolution. Directional positive selection possibly mediated by the immune system operates to a significant extent in the PI sequences, as indicated by the distribution of the positively selected sites in the surface-exposed loops. Thirteen amino acid physicochemical properties seem to drive protein evolution of the PI porins in N. gonorrhoeae.
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