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Nucleic Acids Research Advance Access originally published online on August 12, 2006
Nucleic Acids Research 2006 34(14):3955-3967; doi:10.1093/nar/gkl556
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Nucleic Acids Research, 2006, Vol. 34, No. 14 3955-3967
© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genomics

Comprehensive splice-site analysis using comparative genomics

Nihar Sheth, Xavier Roca, Michelle L. Hastings, Ted Roeder, Adrian R. Krainer and Ravi Sachidanandam*

Cold Spring Harbor Laboratory 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA

*To whom correspondence should be addressed. Tel: +1 516 367 8864; Fax: +1 516 367 8389; Email: sachidan{at}cshl.edu

Received June 7, 2006. Revised July 13, 2006. Accepted July 17, 2006.

We have collected over half a million splice sites from five species—Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana—and classified them into four subtypes: U2-type GT–AG and GC–AG and U12-type GT–AG and AT–AC. We have also found new examples of rare splice-site categories, such as U12-type introns without canonical borders, and U2-dependent AT–AC introns. The splice-site sequences and several tools to explore them are available on a public website (SpliceRack). For the U12-type introns, we find several features conserved across species, as well as a clustering of these introns on genes. Using the information content of the splice-site motifs, and the phylogenetic distance between them, we identify: (i) a higher degree of conservation in the exonic portion of the U2-type splice sites in more complex organisms; (ii) conservation of exonic nucleotides for U12-type splice sites; (iii) divergent evolution of C.elegans 3' splice sites (3'ss) and (iv) distinct evolutionary histories of 5' and 3'ss. Our study proves that the identification of broad patterns in naturally-occurring splice sites, through the analysis of genomic datasets, provides mechanistic and evolutionary insights into pre-mRNA splicing.

Present address: Nihar Sheth, Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, VA 23284-2030, USA

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


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