The genome of malignant rabbit virus (MRV), a newly discovered tumorigenic poxvirus of rabbits, has been analyzed using cloned DNA probes from Shope fibroma virus (SFV) and myxoma virus. Under high stringency conditions for Southern blotting such that SFV probes do not cross-hybridize with myxoma virus DNA, it is demonstrated that greater than 90% of the MRV genome has been derived from myxoma virus, and that approximately 10 kb of SFV-derived sequences have substituted for a similar amount of myxoma sequences. Mapping of the MRV genome indicates that the SFV sequences are present in two regions of the genome, one in each copy of the MRV terminal inverted repeat sequence. Furthermore, fine mapping studies of the integration sites for SFV into the myxoma background show that these SFV sequences are not symmetrical with respect to the left and right genomic termini. At the left end, 4 kb of SFV-derived DNA maps between 6 and 10 kb from the terminus, while at the right end about 5.5 kb of SFV sequences are found to extend at least 1 kb further toward the unique internal sequences. Based on this asymmetrical bipartite distribution of SFV sequences in MRV, a two-stage model to rationalize the origin of MRV is proposed. This model postulates an initial recombination event similar to gene conversion between myxoma and SFV at the right terminus of myxoma, followed by an incomplete transposition of only part of these SFV sequences to the left terminus.
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