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Bioinformatics Advance Access published online on September 3, 2004
Bioinformatics, doi:10.1093/bioinformatics/bti007
Bioinformatics © Oxford University Press 2004; all rights reserved
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Received May 20, 2004
Revised July 29, 2004
Accepted August 26, 2004

Article

Detecting overlapping coding sequences with pairwise alignments

Andrew E. Firth 1 and Chris M. Brown 1*

1 Department of Biochemistry, University of Otago, PO Box 56, Dunedin, New Zealand

* To whom correspondence should be addressed. E-mail: chris.brown{at}otago.ac.nz.


  Abstract

Motivation: Overlapping gene coding sequences (CDSs) are particularly common in viruses but also occur in more complex genomes. Detecting such genes with conventional gene-finding algorithms can be difficult for several reasons. If an overlapping CDS is on the same read-strand as a known CDS, then there may not be a distinct promoter or mRNA. Furthermore, the constraints imposed by double-coding can result in atypical codon biases. However these same constraints lead to particular mutation patterns that may be detectable in sequence alignments.

Results: In this paper we investigate several statistics for detecting double-coding sequences with pairwise alignments - including a new maximum likelihood method. We also develop a model for double-coding sequence evolution. Using simulated sequences generated with the model, we characterize the distribution of each statistic as a function of sequence composition, length, divergence time and double-coding frame. Using these results, we develop several algorithms for detecting overlapping CDSs.

The algorithms are tested on known overlapping CDSs and other overlapping open reading frames (ORFs) in the hepatitis B (HBV), Escherichia coli and Salmonella typhimurium genomes. The algorithms should prove useful for detecting novel overlapping genes - especially short coding ORFs in viruses.

Availability: Programmes may be obtained from the authors.

Supplementary information: http://biochem.otago.ac.nz/double.html.


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