ISIS, the intron information system, reveals the high frequency of alternative splicing in the human genome

• Published in: Nature genetics Vol. 24; no. 4; pp. 340 - 341
• Main Authors: Mattick, John S, Croft, Larry, Schandorff, Soeren, Clark, Francis, Burrage, Kevin, Arctander, Peter
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.04.2000
• Subjects: Alternative Splicing - genetics; Computational Biology; Databases, Factual - trends; DNA microarrays; Exons - genetics; Expressed Sequence Tags; Gene Frequency; Genetic engineering; Genome, Human; Humans; Introns; Introns - genetics; Physiological aspects; Protein Isoforms - genetics; RNA, Messenger - genetics; Australia
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/74153

In recent years, the discovery of many regulatory elements within introns, the recognition of the regulatory potential of intronic and other non-protein coding RNAs, and the concept of a cellular 'ribotype' resulting from differences in RNA processing in different cells and tissues have led to increasing interest in the role of introns' in enhancing eukaryotic genetic complexity, via alternative splicing and as both the recipient and donor of cis-acting and trans-acting elements. To explore the evolution and function of introns in eukaryotes, we have developed an intron sequence information system (ISIS; http://isis.bit.uq.edu.au/) which contains information on over 170,000 spliceosomal introns. Data in ISIS version 1 is based on intron-containing sequences from GenBank release 111. ISIS contains phylogenetic and protein homology categories, information about individual sequences and various bioinformatic analyses of taxonomical groupings of sequences using non-redundant subsets of the data. The database is searchable by Blast, GenBank attributes and elements that we have annotated within introns, and gives graphical views of gene structure and elements such as alternative coding regions, EST matches and repetitive sequences. During analysis of this database, we found many EST matches within sequences annotated as introns, indicating that there are many previously unrecognized alternatively spliced exons, especially as many of these exons are conserved between species. Alternative splicing was first predicted by Walter Gilbert, and subsequently verified by the discovery of cDNA isoforms exhibiting the addition or exclusion of whole or partial exons, although identification of such splice variants has largely occurred on an ad hoc basis. The development of large human EST (partial cDNA) sequence libraries over recent years, however, provides an opportunity to examine the incidence of alternative splicing globally by searching these libraries for exon skipping, exon truncation or inclusion of sequences currently described as intronic.