Structural relationship between the chicken protooncogene c-mil and the retroviral oncogene v-mil.

The avian leukemia and carcinoma inducing retrovirus MH2 contains the novel oncogene v-mil in addition to the cell-derived oncogene v-myc. High-molecular-weight chicken DNA contains sequences closely related to v-mil and also sequences more distantly related to this gene. Several phage clones were isolated by screening of a chicken recombinant DNA library with a v-mil-specific probe in stringent conditions. These clones contain overlapping segments of v-mil-related chicken DNA. Hence, the sequences closely related to v-mil, termed c-mil, appear to represent a single-copy locus of the chicken genome. The close relationship between the cellular and the viral gene was demonstrated by hybridization between c-mil DNA and MH2 viral RNA, or between c-mil DNA and cloned v-mil DNA, and by a comparison of their restriction maps, which revealed total conservation in c-mil DNA of all restriction sites found in v-mil DNA. The c-mil locus spans at least 10 kb, with nine regions of homology to v-mil, ranging in size from about 0.07 to 0.17 kb, interrupted by eight intervening sequences with complexities of about 0.5 to 3.5 kb. Analyses of the cloned chicken c-mil and c-myc loci by nucleic acid hybridization employing specific probes from the mil-myc junction of MH2 proviral DNA revealed that c-mil- and c-myc-related sequences are directly adjacent in the viral genome and that MH2 contains additional 5' c-myc-related sequences not present in the genomes of other leukemia viruses carrying the v-myc oncogene.