Human lipoprotein lipase last exon is not translated, in contrast to lower vertebrates.

We have sequenced the first fish (zebrafish, Brachydanio rerio) lipoprotein lipase (LPL) cDNA clone. Similarities were found in mammalian LPL 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 10 is thus partially translated. These results were confirmed with rainbow trout (Oncorhynchus mykiss). We also investigated whether mammal TGA coded for selenocystein (SeCys), the 21st amino acid, but found that 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 remains to be determined if the "loss" of the C-terminal end of mammalian LPL protein has conferred an advantage in terms of LPL activity or, on the contrary, a disadvantage (e.g., susceptibility to diabetes or atherosclerosis).