BMC Genomics Research article Assessing the number of ancestral alternatively spliced exons in the human genome Rotem Sorek*†1,4, Gideon Dror†2 and Ron Shamir3 BioMed Central Open Access Address: 1Department of Human Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel, 2The Academic College of Tel- Aviv-Yaffo, Tel-Aviv, 64044, Israel, 3School of Computer Science, Tel Aviv University, Tel-Aviv 69073, Israel and 4Genomics Division, One Cyclotron Road, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA Email: Rotem Sorek* - rsorek@lbl.gov; Gideon Dror - gideon@mta.ac.il; Ron Shamir - rshamir@post.tau.ac.il * Corresponding author †Equal contributors Published: 24 October 2006 BMC Genomics 2006, 7:273 doi:10.1186/1471-2164-7-273 This article is available from: http://www.biomedcentral.com/1471-2164/7/273 Received: 19 July 2006 Accepted: 24 October 2006 © 2006 Sorek 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: It is estimated that between 35% and 74% of all human genes undergo alternative splicing. However, as a gene that undergoes alternative splicing can have between one and dozens of alternative exons, the number of alternatively spliced genes by itself is not informative enough. An additional parameter, which was not addressed so far, is therefore the number of human exons that undergo alternative splicing. We have previously described an accurate machine-learning method allowing the detection of conserved alternatively spliced exons without using ESTs, which relies on specific features of the exon and its genomic vicinity that distinguish alternatively spliced exons from constitutive ones. Results: In this study we use the above-described approach to calculate that 7.2% (± 1.1%) of all human exons that are conserved in mouse are alternatively spliced in both species. Conclusion: This number is the first estimation for the extent of ancestral alternatively spliced exons in the human genome. Background In recent years, numerous studies have shown that alter- native splicing is very prevalent in the human genome. Assessing the number of genes that undergo alternative splicing has drawn much attention since the emergence of ESTs as a resource for global alternative splicing analysis. Early studies estimated this number at 35% [1] 38% [2] and 42% [3] while recent studies present numbers as high as 59% [4] 74% [5] and even higher [6,7]. However, there is an ongoing debate as to how many of these predicted splice variants are functional, and how many are the result of aberrant splicing (or 'noise') [8,9]. In addition, ESTs provide only a sample of the human transcriptome, and many splice variants (including evolutionarily conserved ones) are not represented in public EST databases. The number of human genes that undergo alternative splicing, therefore, remains elusive. But does this number reveal the full picture of the tran- scriptome complexity? Some genes can produce extremely high number of transcripts, while others produce only two or three variants. For example, the drosophila DSCAM gene, which harbors 95 alternatively spliced exons, can theoretically produce up to 38,016 different transcripts. This number of transcripts, produced from this single gene, is twice the number of genes in the entire fly genome. Therefore, the number of exons that undergo alternative splicing is a crucial parameter, and gives new, Page 1 of 8 (page number not for citation purposes)