HUMAN LIPOPROTEIN-LIPASE LAST EXON IS NOT TRANSLATED, IN CONTRAST TO LOWER-VERTEBRATES

We have sequenced the first fish (zebrafish, Brachydanio rerio) lipopr otein lipase (LPL) cDNA clone. Similarities were found in mammalian LP L cDNA, but the codon spanning the last two exons (which is thus split by the last intron) is AGA (Arg) as opposed to TGA in mammals. Exon 1 0 is thus partially translated. These results were confirmed with rain bow trout (Oncorhynchus mykiss). We also investigated whether mammal T GA coded for selenocystein (SeCys), the 21st amino acid, but found tha t this was not the case: TGA does not encode SeCys but is a stop codon . It thus appears that the sense codon AGA (fish) has been transformed into a stop codon TGA (human) during the course of evolution. It rema ins to be determined if the ''loss'' of the C-terminal end of mammalia n LPL protein has conferred an advantage in terms of LPL activity or, on the contrary, a disadvantage (e.g., susceptibility to diabetes or a therosclerosis).