ALTERNATIVE SPLICING IN LECITHIN-CHOLESTEROL ACYLTRANSFERASE MESSENGER-RNA - AN EVOLUTIONARY PARADIGM IN HUMANS AND GREAT APES

Lecithin:cholesterol acyltransferase (LCAT), an important enzyme affec ting reverse cholesterol transport, is expressed in liver and cultured fibroblasts. Sequencing of LCAT cDNA clones demonstrated the coexiste nce of two mRNA products. In addition to the normal transcript, we ide ntified an alternate message with a splice-mediated insertion of a 95 bp Alu cassette at the junction of exons 5 and 6. In humans, the alter nate transcript represents 5-20% of the complete LCAT message in cultu red fibroblasts and liver. It is present in humans and the great apes but not in lesser apes (gibbon, siamang) or lower-order primates (e.g. , old or new world monkeys). Sequencing of intron 5 of the LCAT locus in several primates revealed a G-->A transition at the splice donor re cognition site in the Alu repeat of the gibbon and a G-->A substitutio n in the last position of the 95 bp Alu sequence of the rhesus monkey, an old world monkey. Both substitutions have been associated with exo n skipping in other genes. These results demonstrate that alternative splicing of LCAT mRNA is variant among primates and suggest a potentia l role of Alu elements in the evolutionary diversity of proteins. (C) 1997 Elsevier Science B.V.