ALU SEQUENCES IN THE CODING REGIONS OF MESSENGER-RNA - SOURCE OF PROTEIN VARIABILITY

Dispersion of repetitive sequence elements is a source of genetic vari ability that contributes to genome evolution. Alu elements, the most c ommon dispersed repents in the human genome, catt cause genetic diseas es by several mechanisms, including de novo Alu insertions asd splicin g of intragenic Alu elements into mRNA. Such mutations might contribut e positively to protein evolution if they are advantageous or neutral. To test this hypothesis, we searched the literature and sequence data bases for examples of protein-coding regions that contain Alu sequence s: 17 Alu 'cassettes' inserted within 15 different coding sequences we re found. In three instances, these events caused genetic diseases; th e possible functional significance of the other Alu-containing mRNAs i s discussed. Our analysis suggests that splice-mediated insertion of i ntronic elements is the major mechanism by which Alu segments are intr oduced into mRNAs.