HIGH SEQUENCE SIMILARITY WITHIN RAS EXON-1 AND EXON-2 IN DIFFERENT MAMMALIAN-SPECIES AND PHYLOGENETIC DIVERGENCE OF THE RAS GENE FAMILY

We have determined the canine and feline N-, K-, and H-ras gene sequen ces from position +23 to +270 covering exons I and II which contain th e mutational hot spot codons 12, 13, and 61. The results were used to assess the degree of similarity between ras gene DNA regions containin g the critical domains affected in neoplastic disorders in different m ammalian species. The comparative analyses performed included human, c anine, feline, murine, rattine, and, whenever possible, bovine, lepori ne (rabbit), porcelline (guinea pig), and mesocricetine (hamster) rns gene sequences within the region of interest. Comparison of feline and canine nucleotide sequences with the corresponding regions in human D NA revealed a sequence similarity greater than 85% to the human sequen ce. Contemporaneous analysis of previously published ras DNA sequences from other mammalian species showed a similar degree of homology to h uman DNA. Most nucleotide differences observed represented synonymous changes without effect on the amino acid sequence of the respective pr oteins. For assessment of the phylogenetic evolution of ms gene family , a maximum parsimony dendrogram based on multiple sequence alignment of the common region of exons I and II in the N-, K-, and H-ras genes was constructed. Interestingly, a higher substitution rate among the H -ras genes became apparent, indicating accelerated sequence evolution within this particular clade. The most parsimonious tree clearly shows that the duplications giving rise to the three ras genes must have oc curred before the mammalian radiation.