Genetics. Published Articles Ahead of Print: February 19, 2006, Copyright © 2006
doi:10.1534/genetics.105.054601


A more recent version of this article appeared on April 1, 2006.

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Analysis of Core Housekeeping and Virulence Genes Reveals Cryptic Lineages of Clostridium perfringens that are Associated with Distinct Disease Presentations

Alejandro P. Rooney 1*, James L Swezey 1, Robert Friedman 2, David W. Hecht 3 and Carol W Maddox 4

1 USDA Agricultural Research Service
2 University of Connecticut
3 Loyola University Medical Center
4 University of Illinois

* To whom correspondence should be addressed. E-mail: rooney{at}ncaur.usda.gov.

Submitted on December 12, 2005
Revised on January 22, 2006
Accepted on 3 February 2006


Abstract

Clostridium perfringens is an important human and animal pathogen that causes a number of diseases that vary in their etiology and severity. Differences between strains regarding toxin gene composition and toxin production partly explain why some strains cause radically different diseases than others. However, it does not provide a complete explanation. The purpose of this study was to determine if there is a phylogenetic component that explains the variance in C. perfringens strain virulence by assessing patterns of genetic polymorphism in genes (colA gyrA, plc, pfoS, and rplL) that form part of the core genome in 248 type A strains. We found that purifying selection plays a central role in shaping the patterns of nucleotide substitution and polymorphism in both housekeeping and virulence genes. In contrast, recombination was found to be a significant factor only for the virulence genes plc and colA and the housekeeping gene gyrA. Finally, we found that the strains grouped into 5 distinct evolutionary lineages that show evidence of host-adaptation and the early stages of speciation. The discovery of these previously unknown lineages and their association with distinct disease presentations carries important implications for human and veterinary clostridial disease epidemiology and provides important insights into the pathways through which virulence has evolved in C. perfringens.

Key Words: Clostridium perfringens, adaptive evolution, core genome, recombination, speciation