Alu-containing exons are alternatively spliced

Alu repetitive elements are found in 44 million copies in the human genome, comprising more than one-tenth of it. Numerous studies describe exonizations of Alu elements, that is, splicing-mediated insertions of parts of Alu sequences into mature mRNAs. To Study the connection between the exonization of Alu elements and alternative splicing, we used a database of ESTs and cDNAs aligned to the human genome. We compiled two exon sets, one of 1176 alternatively spliced internal exons, and another of 4151 constitutively spliced internal exons. Sixty one alternatively spliced internal exons (5.2%) had a significant hit to ail Alu sequence, but none of the constitutively spliced internal exons had such a hit. The vast majority (84%) of the AN-containing exons that appeared within the coding region of mRNAs Caused a frame-shift or a premature termination codon. Alu-containing exons were included in transcripts at lower frequencies than alternatively spliced exons that do not contain ail Alu sequence. These results indicate that internal exons that contain ail AN sequence are predominantly, if not exclusively, alternatively spliced. Presumably, evolutionary events that Cause a constitutive insertion of an Alu sequence into an mRNA are deleterious and selected against.