Published online 2 December 2004
Nucleic Acids Research, Vol. 32 No. 21 © Oxford University Press 2004; all rights reserved
Identification of genes with fast-evolving regions in microbial genomes
1 Bioinformatics Graduate Program and 2 Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA and 3 New England Biolabs, Beverly, MA 01915, USA
* To whom correspondence should be addressed. Tel: +1 617 358 1845; Fax: +1 617 353 6766; Email: kasif{at}bu.edu
Present address: Yu Zheng, New England Biolabs, 32 Tozer Road, Beverly, MA 01915, USA
Received August 30, 2004; Revised and Accepted October 25, 2004
Complete sequences of multiple strains of the same microbial species provide an invaluable source for studying the evolutionary dynamics between orthologous genes over a relatively short time scale. Usually the intensity of the selection pressure is inferred from a comparison between the nonsynonymous substitution rate and the synonymous substitution rate. In this paper, we propose an alternative method for detecting genes with one or more fast-evolving regions from pairwise comparisons of orthologous genes. Our method looks for regions with overrepresented nonsynonymous mutations along the alignment, and requires a higher nonsynonymous evolution rate in those regions than the neutral evolution rate. It identifies gene targets under intensive selection pressure that are not detected from the conventional rate comparison analysis. For those identified genes with known annotations, most of them have a clear role in processes such as bacterial defense and hostpathogen interactions. Gene sets reported from our method provide a measure of the phenotypic divergence between two closely related genomes.
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