Detecting overlapping coding sequences with pairwise alignments

Bioinformatics
Andrew E Firth, Chris M Brown

Abstract

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. 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 were tested on known overlapping CDSs and other overlapping open reading frames (ORFs) in the hepatitis B virus (HBV), Escherichia coli and Salmonella typhimurium genomes. The algorithms should prove ...Continue Reading

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Citations

Sep 8, 2010·Journal of Molecular Evolution·Niv Sabath, Dan Graur
Apr 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Betty Y-W ChungAndrew E Firth
Apr 15, 2006·Bioinformatics·Stephen McCauley, Jotun Hein
Mar 8, 2007·Bioinformatics·Saskia de GrootJotun Hein
Oct 9, 2007·Bioinformatics·Stephen McCauleyJotun Hein
Jul 24, 2012·Molecular Biology and Evolution·Niv SabathDavid Karlin
Sep 6, 2007·Genome Research·Robert BelshawAndrew Rambaut
Feb 18, 2006·BMC Bioinformatics·Andrew E Firth, Chris M Brown
Mar 24, 2006·Virology Journal·Michael J AllenWilliam H Wilson
Nov 18, 2009·Virology Journal·Monica CliffordChris Upton
Nov 10, 2009·Trends in Microbiology·Thomas SchoenfeldDavid Mead
Aug 25, 2015·The Journal of General Virology·Patrick C Y WooKwok-Yung Yuen
Oct 25, 2011·PloS One·Mourad BelhouchetHoussam Attoui
Aug 14, 2018·Molecular Biology and Evolution·Timothy E SchlubEdward C Holmes
Oct 11, 2017·PLoS Neglected Tropical Diseases·Laura E Kirby, Donna Koslowsky
Apr 24, 2014·Virus Genes·Adriana Ribeiro Silva BatistaTatsuya Nagata
Sep 17, 2018·BMC Bioinformatics·Rohit KongariRy Young
May 21, 2021·Nature·Jessica Sook Yuin HoIvan Marazzi

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