Nucleotide sequence of two overlapping myc-related genes in avian carcinoma virus OK10 and their relation to the myc genes of other viruses and the cell.

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Abstract
Avian carcinoma virus OK10 has the genetic structure gag-.DELTA.pol-myc-.DELTA.env. It shares the transformation-specific myc sequence with 3 other avian carcinoma viruses (MC29, MH2, CMII) and also with a normal chicken gene proto-myc and the gag, pol and env elements with non-transforming retroviruses. Unlike the other myc-containing viruses, which synthesize singular myc proteins, OK10 synthesizes 2 different myc-related proteins of 200 and 57 kDa (kilodalton). The myc region of an infectious OK10 provirus was sequenced here to investigate how OK10 synthesizes 2 different proteins from the same myc domain and to identify characteristic differences between the normal proto-myc gene and the myc-related viral transforming genes. It was found that the 1.6-kilobase myc domain of OK10 is colinear and coterminal with the myc domains of MC29, MH2, and the terminal 2 exons of proto-myc. It is preceded by the same splice acceptor as the myc sequence of MH2 and as the 2nd proto-myc exon. From this and the known structure of retroviruses, it follows that the OK10 gene encoding the 57-kDa protein is discontinuous with a small 5'' exon that includes 6 gag codons and a large 3'' myc exon (.delta.gag-myc). This gene and the .delta.gag-myc gene of MH2 are isogenic. The proto-myc-derived intron preceding the myc domain of OK10 is in the same reading frame as the adjacent .DELTA.pol and myc domains and, hence, is part of the gag-.DELTA.pol-myc gene encoding the 200-kDa protein. Sequence comparisons with proto-myc and MC29 and MH2 indicate that there are no characteristic mutations that set apart the viral myc domains from proto-myc. Thus, transforming function of viral myc-related genes correlates with the lack of a viral equivalent of the 1st proto-myc exon(s) and conjugation of the viral myc domains with large or small retroviral genetic elements rather than with specific point mutations. Because OK10 and MH2 each contain 2 genes with potential transforming function (namely, .delta.gag-myc and gag-.DELTA.pol-myc or .DELTA.gag-mht, respectively), it remains to be determined whether the .delta.gag-myc genes have transforming function on their own or need helper genes. The possible helper requirement cannot be very specific because the 2 potential helper genes are very different.