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Nucleic Acids Research 2004 32(21):6347-6357; doi:10.1093/nar/gkh935
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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

Yu Zheng1, Richard J. Roberts3 and Simon Kasif1,2,*

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 host–pathogen interactions. Gene sets reported from our method provide a measure of the phenotypic divergence between two closely related genomes.


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