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Avian carcinoma virus MH2 has been grouped together with MC29, CMII, and OK10, because all of these viruses share a transformation-specific sequence termed myc. A 5.2-kilobase (kb) DNA provirus of MH2 has been molecularly cloned. The complete genetic structure of MH2 is 5'-delta gag(1.9-kb)-mht(1.2-kb)-myc(1.3-kb)-delta env(?) and noncoding c-region (0.2-kb)-3'. delta gag, delta env, and c are genetic elements shared with nondefective retroviruses, whereas mht is a unique, possibly MH2 transformation-specific, sequence. Hybridizations with normal chicken DNA and cloned chicken c-myc DNA indicate that the mht sequence probably derives from a normal cellular gene that is distinct from the c-myc gene. The genetic structure of MH2 suggests that the delta gag and mht sequences function as a hybrid gene that encodes the p100 putative transforming protein. The myc sequence of MH2 appears to encode a second transforming function. Therefore, it seems that MH2 contains two genes with possible oncogenic function, whereas MC29, CMII, and OK10 each carries a single hybrid delta gag-myc transforming gene. It is remarkable that, despite these fundamental differences in their primary structures and mechanisms of gene expression, MH2 and MC29 have very similar oncogenic properties.

A common cellular sequence was independently transduced by avian carcinoma virus MH2 (v-mht) and murine sarcoma virus (MSV) 3611 (v-raf). Comparison of the nucleotide sequences of v-mht and v-raf revealed a region of homology that extends over 969 nucleotides. The homology between the corresponding amino acids was about 95 percent with only 19 of 323 amino acids being different. With this example, 5 of the 19 known different viral onc genes have been observed in viruses of different taxonomic groups. These data indicate that (i) the number of cellular proto-onc genes is limited because, like other viruses of different taxonomic groups, MH2 and MSV 3611 have transduced the same onc gene-specific sequences from different cell species and (ii) that specific deletion and linkage of the same proto-onc sequences to different viral vector elements affect the oncogenic potential of the resulting viruses. The difference in transformation capabilities of MH2 and MSV 3611 serves as an example.

Agag is a partial retroviral core protein gene, mht and myc are cell-derived MH2-specific sequences, and c is the 3'-terminal retroviral vector sequence. Here we have determined the nucleotide sequence of 3.5 kb from the 3' end of Agag to the 3' end of molecularly cloned proviral MH2 DNA, in order to elucidate the genetic structure of the virus and to compare it with other mht-and myc-containing oncogenic viruses as well as with the chicken proto-myc gene. The following results were obtained: (i) Agag-mht forms a hybrid gene with a contiguous

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The entire intervening sequence of Tetrahymena thermophila ribosomal DNA has been determined. It is 413 nucleotides long and has the same splice junctions as those in T. pigmentosa. There is 93% homology between the intervening sequences in the two species, and 100% homology between their adjacent 26S RNA coding regions.

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Most directly oncogenic retroviruses contain single, autonomous transforming (onc) genes (1). However, three oncogenic retroviruses contain two genes with oncogenic potential, namely the avian carcinoma viruses MH2 (2-5) and OK10 (6, 7) and avian erythroblastosis virus (AEV) (8, 9). The 5.5-kilobase (kb) RNA genome of MH2 (10) has the genetic structure Agag-mht-myc (2-5). One of the two genes with potential transforming function encoded by MH2 is a 3-kb Agag-mht gene, defined by a p100 protein product (11). A close structural relative of this gene (5, 12) is the only transforming gene of murine sarcoma virus MSV 3611 (13).The other MH2 gene is a myc-related gene, termed 8gag-myc, which is discontiguous. This gene includes a gag-derived 5' exon of only six gag codons (therefore 8gag) and a 3' 1.6-kb myc exon that is colinear with the two 3'-terminal exons of chicken proto-myc (5, 14). This gene is expressed via a subgenomic 2.6-kb mRNA as a 57,000-dalton (p57) protein product (15-18). The 7.5-kb RNA genome of OK10 virus (19) contains two overlapping myc-related genes (7); a contiguous gag-Apol-myc gene, which encodes a p200 protein; and a discontiguous 8gag-myc gene, which as in MH2 is also expressed as a subgenomic 3.5-kb mRNA encoding a p57protein (6,17,18 Here we analyze MH2 to determine whether it could serve as a model for multigene carcinogenesis. Several lines of evidence indicate that the 8gag-myc gene of MH2 is necessary for oncogenicity and that it transforms fibroblasts without Agag-mht as helper gene. (1) The 8gag-myc gene of MH2 is shared by MH2 and OK10 (7). Since both viruses have similar oncogenic spectra yet each has a specific second gene with potential transforming function, it follows that 8gag-myc is essential for common oncogenic properties (7).(ii) A study that has isolated MH2-transformed fibroblasts that express high levels of the 8gag-myc product p57 but no detectable Agag-mht product pl00 has concluded that p57 is sufficient for transforming function (15 6389The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.