ABSTRACT

The ras oncogenes are highly conserved in evolution. Homologs of these genes have been found in many eukaryotes, including unicellular 18 , 23 , 32 , 75 , 78 and complex multicellular organisms. 26 , 40 70 It is likely that ras homologs will be found in all eukaryotic organisms. Certainly there are no other oncogenes presently known that are as highly conserved. The degree of identify between the mammalian oncogenic RAS proteins and the RAS proteins of the yeasts Saccharomyces cerevisiae (RASI and RAS2) and Schizosaccharomyces pombe (ras1) in the N terminal halves of the molecules is about 90%. To put this into perspective, the degree of identity between the cAMP-dependent protein kinase regulatory subunits from yeasts and mammals is in the range of 50%. 95 These subunits bind two molecules of cAMP apiece, dimerize, bind the catalytic sub-unit, release the catalytic subunit from inhibition upon binding cAMP, and retain the ability to interact with the catalytic subunit of the divergent organisms. 42 , 111 From this example it is reasonable to infer that the level of conservation of primary structure observed for RAS is associated with the conservation of many biochemical functions. This inference is correct.