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. 1981 Sep;39(3):758–776. doi: 10.1128/jvi.39.3.758-776.1981

src Genes of Ten Rous Sarcoma Virus Strains, Including Two Reportedly Transduced from the Cell, Are Completely Allelic; Putative Markers of Transduction Are Not Detected

Wen-Hwa Lee 1, Michael Nunn 1, Peter H Duesberg 1
PMCID: PMC171309  PMID: 6270350

Abstract

The src genes of different Rous sarcoma virus (RSV) strains have been reported to be highly conserved by some investigators using RNA-cDNA hybridization, whereas others using oligonucleotide, peptide, and serological analyses have judged src genes to be variable in 30 to 50% of the respective markers. Moreover, distinctive src oligonucleotides and peptides of so-called recovered RSVs (rRSV's) whose src genes were reported to be experimentally transduced from the cell are thought to represent specific markers of host-derived src sequences. By contrast, we have pointed out previously that these markers may represent point mutations of parental equivalents. Here we have compared the src-specific sequences of eight RSV strains and of two rRSV's to each other and to a molecular clone of the src-related chicken locus. Our comparisons are based on RNase T1-resistant oligonucleotides of RNA hybridized to src-specific cDNA, which was prepared by hybridizing RSV cDNA with RNA of isogenic src deletion mutants, or to a cloned cellular src-related DNA. All of the approximately 20 src-oligonucleotides of a given RSV strain were recovered by src-specific cDNA's of all other RSV strains or by cellular src-related DNA. The number of oligonucleotides varied slightly with the length of the src deletion used to prepare src-specific cDNA, thus providing a measure for src deletion mutants. Our data indicate that the src genes of all RSV strains tested, including the two reportedly transduced from the cell, are about 98% conserved and completely allelic with only scattered single nucleotide differences in certain variable regions which are subject to point mutations. Hence, based on the src oligonucleotide markers analyzed by us and others, we cannot distinguish between a cellular and viral origin of rRSV's. However, the following are not compatible with a cellular origin of rRSV's. (i) The only putative oligonucleotide marker which is exclusively shared by the two rRSV's studied and which differs from a parental counterpart in a single base was not detectable in cellular src-related DNA. (ii) The number of different allelic src markers observed by us and others in rRSV's was too large to derive from one or two known cellular src-related loci. (iii) The known absence of linkage of the cellular src-related locus with other virion sequences was extended to all non-src oligonucleotides, including some mapping directly adjacent to src. This is difficult to reconcile with the claim that transformation-defective, partial src deletion mutants of RSV which contain both, one, or, as we show here, possibly no src termini nevertheless transduce at the same frequencies, even though homologous, single or double illegitimate recombinations would be involved. Given (i) our evidence that src genes are subject to point mutation under selective conditions similar to those prevailing when rRSV's were generated and (ii) the lack of absolute evidence for the clonal purity of the transformation-defective, partial src deletion mutants of RSV used to generate rRSV's, we submit that the src genes of rRSV's could have been generated by cross-reactivation of nonoverlapping src deletions or mutation of src variants possibly present in transformation-defective, partial src deletion mutants of RSV. To prove experimental transduction, unambiguous markers need to be identified, or it would be necessary to generate rRSV's with molecularly cloned transformation-defective, partial src deletion mutants of RSV. Although our evidence casts doubt on the idea that specific src sequences of rRSV's originated by transduction, the close relationship between viral src and cellular src-related sequences argues that src genes originated at one time in evolution from the cell by events that involved illegitimate recombination and deletion of non-src sequences that interrupt the cellular src locus.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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