Simian virus 40 illegitimate recombination occurs near short direct repeats

We have analysed nucleotide sequences at the junction between simian virus 40 (SV40) and cellular DNA in the Fisher rat transformed line tsA30-N2. This line contains a single insertion of one complete SV40 genome with a terminal duplication of 267 nucleotides, the recombination sites being located at nucleotides 439 and 705 in the late region of SV40. These two positions are located within short direct repeats in the virus genome. In order to test the significance of such repeats with respect to illegitimate recombination events, we analysed two series of published sequences of SV40 recombination sites: the first one consists of eight SV40 insertion endpoints derived from four SV40-transformed cell lines; the second one consists of 18 junction points from SV40 evolutionary variants. Our analysis demonstrates that in both cases, recombination preferentially takes place near short direct repeats in the virus genome. A model involving a "slipped mispairing" mechanism is proposed in order to account for this finding.