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MBE Advance Access published online on August 22, 2006

Molecular Biology and Evolution, doi:10.1093/molbev/msl092
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© The Author 2006. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted August 16, 2006

Research Article

Molecular Evolution of the tprC, D, I, K, G, and J Genes in the Pathogenic Genus Treponema

R.R. Gray 1, C.J. Mulligan 1 *, B.J. Molini 2, E.S. Sun 3, L. Giacani 2, C. Godornes 2, A. Kitchen 1, S.A. Lukehart 4, and A. Centurion-Lara 4

1 Department of Anthropology, University of Florida
2 Department of Medicine, University of Washington
3 Department of Pathobiology, University of Washington
4 Department of Medicine, University of Washington; Department of Pathobiology, University of Washington

* To whom correspondence should be addressed.
C.J. Mulligan, E-mail: mulligan{at}anthro.ufl.edu


   Abstract

We investigated the evolution of six genes from the Treponema pallidum repeat (tpr) gene family, which encode potential virulence factors and are assumed to have evolved through gene duplication and gene conversion events. The six loci (tprC, D, G, J, I, and K) were sequenced and analyzed in several members of the genus Treponema, including the three subspecies of human T. pallidum (T. p. subsp. pallidum, pertenue, and endemicum), T. paraluiscuniculi (rabbit syphilis), and the unclassified Fribourg-Blanc (simian) isolate. Phylogenetic methods, recombination analysis, and measures of nucleotide diversity were used to investigate the evolutionary history of the tpr genes. Numerous instances of gene conversion were detected by all three methods including both homogenizing gene conversion that involved the entire length of the sequence as well as site-specific conversions that affected smaller regions. We determined the relative age and directionality of the gene conversion events whenever possible. Our data are also relevant to a discussion of the evolution of the treponemes themselves. Higher levels of variation exist between the human subspecies than within them, supporting the classification of the human treponemes into three subspecies. In contrast to published theories, the divergence and diversity of T. pallidum subsp. pertenue relative to the other subspecies does not support a much older origin of yaws at the emergence of modern human, nor is the level of divergence seen in T. pallidum subsp. pallidum consistent with a very recent (<500 years) origin of this subspecies. In general, our results demonstrate that intra-genomic recombination has played a significant role in the evolution of the studied tpr genes and emphasize that efforts to infer evolutionary history of the treponemes can be complicated if past recombination events are not recognized.

Keywords: Treponema; tpr genes; phylogeny; gene conversion; evolution; syphilis.
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