An Alternative-Exon Database and Its Statistical Analysis

We compiled a comprehensive database of alternative exons from the literature and analyzed them statistically. Most alternative exons are cassette exons and are expressed in more than two tissues. Of all exons whose expression was reported to be specific for a certain tissue, the majority were expressed in the brain. Whereas the length of constitutive exons follows a normal distribution, the distribution of alternative exons is skewed toward smaller ones. Furthermore, alternative-exon splice sites deviate more from the consensus: their 3′ splice sites are characterized by a higher purine content in the polypyrimidine stretch, and their 5′ splice sites deviate from the consensus sequence mostly at the +4 and +5 positions. Furthermore, for exons expressed in a single tissue, adenosine is more frequently used at the -3 position of the 3′ splice site. In addition to the known AC-rich and purine-rich exonic sequence elements, sequence comparison using a Gibbs algorithm identified several motifs in exons surrounded by weak splice sites and in tissue-specific exons. Together, these data indicate a combinatorial effect of weak splice sites, atypical nucleotide usage at certain positions, and functional enhancers as an important contribution to alternative-exon regulation.