Comprehensive splice-site analysis using comparative genomics.
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.
Sheth
Nihar
N
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Roca
Xavier
X
Hastings
Michelle L
ML
Roeder
Ted
T
Krainer
Adrian R
AR
Sachidanandam
Ravi
R
D000818:Animals; D017360:Arabidopsis / Q000235:genetics; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics; D017124:Conserved Sequence; D030561:Databases, Nucleic Acid; D004331:Drosophila melanogaster / Q000235:genetics; D019143:Evolution, Molecular; D023281:Genomics / Q000379:methods*; D006801:Humans; D020407:Internet; D007438:Introns; D010802:Phylogeny; D022821:RNA Splice Sites; D012984:Software
D022821:RNA Splice Sites