EXPRESSION OF RAS GENES IN RAINBOW-TROUT LIVER

Members of the ras gene family have been studied in a variety of species. Two ras genes expressed in the normal liver of rainbow trout, ras-1 and ras-2 as well as a portion of a genomic ras-1 allele, are described for the first time in this report. Over 500 bp of trout ras-1 and at least 300 bp of trout ras-2 genes expressed in normal liver have been sequenced; DNA homology to the human ras genes ranges from 76.8% to 87.1%. The base changes resulting from over 400 million years of evolutionary divergence between the species were primarily silent, with few changes in protein sequence. The partial DNA sequence of the genomic ras-1 allele has 86.8% homology to the first two exons of human c-Ha-ras, and its intron has several conserved sequences characteristic of vertebrate intron-exon junctions. However, the predicted amino acid sequence of trout ras-1 differs at only one of the first 172 amino acid residues from human c-Ki-ras with the alternate exon 4b. Since trout ras-1 differs at 17 and 18 residues from the human c-N-ras and c-Ha-ras proteins, respectively, over this region, we conclude that trout ras-1 is a c-Ki-ras gene. The highly conserved nature of this gene suggests that the ras p21 protein has identical functions in normal and neoplastic cells among higher and lower vertebrates.