Human-Proto-Oncogene Nucleotide Sequences Corresponding to the Transforming Region of Simian Sarcoma Virus

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Abstract
The nucleotide sequences of the 5 regions within the normal human cellular locus (c-sis) that correspond to the entire transforming region of the simian sarcoma virus (SSV) genome (v-sis) were determined. The regions are bounded by acceptor and donor splice sites and, except for region 6, resemble exons. Region 6 lacks a 3'' donor splice site and terminates -5 base pairs from the 3'' v-sis-helper-viral junction. This is consistent with a model proposing that SSV was generated by recombination between proviral DNA of simian sarcoma associated virus and protosis, and that introns were spliced out subsequently from a fused viral-sis mRNA. This also suggests that the 3'' recombination occurred within an exon of the woolly monkey (Lagothrix) genome. The open reading frames predicting the v-sis and c-sis gene products coincide with the stop codon of c-sis located 123 nucleotides into the 5th region of homology. The overall nucleotide homology was 91% with substitutions mainly in the 3rd codon positions within the open reading frame and with greatest divergence within the untranslated 3'' portion of the sequences. The predicted protein products for v-sis and c-sis are 93% homologous. The predicted c-sis gene product is identical in 31 of 31 amino acids to one of the published sequences of platelet-derived growth factor. Thus, c-sis encodes 1 chain of human platelet-derived growth factor.