Rates of evolution of the retroviral oncogene of Moloney murine sarcoma virus and of its cellular homologues

Abstract

A method is proposed for computing the rates of nucleotide substitution for an oncogene of a retrovirus (v-onc), its cellular homologue (c-onc), and the retrovirus genome simultaneously. The method has been applied to DNA sequences of the v-mos gene of Moloney murine sarcoma virus (Mo-MuSV) and the c-mos and gag genes of Mo-MuSV and Moloney murine leukemia virus (Mo-MuLV). The rates of nucleotide substitution for c-mos, the gag gene, and v-mos are estimated to be 1.71 x 10-9, 6.3 x 10-4, and 1.31 x 10-3 per site per year, respectively. The rate of evolution of c-mos is comparable to that of many functional genes in DNA genomes, suggesting some important biological function played by cellular oncogenes. The rates of nucleotide substitution in the v-mos and gag genes are very high and are similar to those of RNA viral genes such as the hemagglutinin and neuraminidase genes in the influenza A virus. Thus, oncogenes seem to exemplify a general feature of genome evolution: the rate of evolution of RNA genomes can be more than a million times greater than that of DNA genomes because of a high mutation rate in the RNA genome.