BMC Genomics Research article Bioinformatics prediction of overlapping frameshifted translation products in mammalian transcripts Sebastien Ribrioux*1, Adrian Brüngger2, Birgit Baumgarten3, Klaus Seuwen3 and Markus R John3 Address: 1Genedata AG, Maulbeerstrasse 46, CH-4016 Basel, Switzerland, 2Basilea Pharmaceutica AG, Grenzacherstrasse 487, CH-4005 Basel, Switzerland and 3Novartis Institutes for Biomedical Research, CH-4002 Basel, Switzerland Email: Sebastien Ribrioux* - sebastien.ribrioux@gmail.com; Adrian Brüngger - adrian.bruengger@basilea.com; Birgit Baumgarten - birgit.baumgarten@novartis.com; Klaus Seuwen - klaus.seuwen@novartis.com; Markus R John - markus.john@novartis.com * Corresponding author BioMed Central Open Access Published: 6 March 2008 BMC Genomics 2008, 9:122 doi:10.1186/1471-2164-9-122 This article is available from: http://www.biomedcentral.com/1471-2164/9/122 Received: 14 June 2007 Accepted: 6 March 2008 © 2008 Ribrioux et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Exceptionally, a single nucleotide sequence can be translated in vivo in two different frames to yield distinct proteins. In the case of the G-protein alpha subunit XL-alpha-s transcript, a frameshifted open reading frame (ORF) in exon 1 is translated to yield a structurally distinct protein called Alex, which plays a role in platelet aggregation and neurological processes. We carried out a novel bioinformatics screen for other possible dual-frame translated sequences, based on comparative genomics. Results: Our method searched human, mouse and rat transcripts in frames +1 and -1 for ORFs which are unusually well conserved at the amino acid level. We name these conserved frameshifted overlapping ORFs 'matreshkas' to reflect their nested character. Select findings of our analysis revealed that the G-protein coupled receptor GPR27 is entirely contained within a frame -1 matreshka, thrombopoietin contains a matreshka which spans ~70% of its length, platelet glycoprotein IIIa (ITGB3) contains a matreshka with the predicted characteristics of a secreted peptide hormone, while the potassium channel KCNK12 contains a matreshka spanning >400 amino acids. Conclusion: Although the in vivo existence of translated matreshkas has not been experimentally verified, this genome-wide analysis provides strong evidence that substantial overlapping coding sequences exist in a number of human and rodent transcripts. Background Overlapping translated open reading frames (tORFs) are usually associated with genomes under selection pressure to remain compact, such as those of viruses. However, such overlaps also exist in mammals. For example in human, an exon is shared by the INK4A and ARF genes and is translated in different frames over 317 bases [1]. Similarly, a transcript fusion between the human EIF4EBP3 and MASK genes results in the translation of 172 bases in two different frames [2]. An alternative splice variant of insulin-like growth factor 1 (IGF-I), called mechano-growth-factor (MGF), contains a frameshift which leads to translation of overlapping reading frames Page 1 of 16 (page number not for citation purposes)