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Genes of Ten Rous Sarcoma Virus Strains, Including Two Reportedly Transduced from the Cell, Are Completely Allelic; Putative Markers of Transduction Are Not Detected
Authors: Lee Wen-Hwa , Nunn Michael , Duesberg Peter H. 
Published: January 2020

The
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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
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genes to be variable in 30 to 50% of the respective markers. Moreover, distinctive
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oligonucleotides and peptides of so-called recovered RSVs (rRSV's) whose
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genes were reported to be experimentally transduced from the cell are thought to represent specific markers of host-derived
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sequences. By contrast, we have pointed out previously that these markers may represent point mutations of parental equivalents. Here we have compared the
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-specific sequences of eight RSV strains and of two rRSV's to each other and to a molecular clone of the
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-related chicken locus. Our comparisons are based on RNase T
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-resistant oligonucleotides of RNA hybridized to
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-specific cDNA, which was prepared by hybridizing RSV cDNA with RNA of isogenic
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deletion mutants, or to a cloned cellular
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-related DNA. All of the approximately 20
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-oligonucleotides of a given RSV strain were recovered by
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-specific cDNA's of all other RSV strains or by cellular
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-related DNA. The number of oligonucleotides varied slightly with the length of the
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deletion used to prepare
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-specific cDNA, thus providing a measure for
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deletion mutants. Our data indicate that the
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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
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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
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-related DNA. (ii) The number of different allelic
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markers observed by us and others in rRSV's was too large to derive from one or two known cellular
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-related loci. (iii) The known absence of linkage of the cellular
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-related locus with other virion sequences was extended to all non-
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oligonucleotides, including some mapping directly adjacent to
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. This is difficult to reconcile with the claim that transformation-defective, partial
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deletion mutants of RSV which contain both, one, or, as we show here, possibly no
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termini nevertheless transduce at the same frequencies, even though homologous, single or double illegitimate recombinations would be involved. Given (i) our evidence that
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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
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deletion mutants of RSV used to generate rRSV's, we submit that the
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genes of rRSV's could have been generated by cross-reactivation of nonoverlapping
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deletions or mutation of
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variants possibly present in transformation-defective, partial
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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
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deletion mutants of RSV. Although our evidence casts doubt on the idea that specific
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sequences of rRSV's originated by transduction, the close relationship between viral
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and cellular
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-related sequences argues that
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genes originated at one time in evolution from the cell by events that involved illegitimate recombination and deletion of non-
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sequences that interrupt the cellular
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locus.