Evidence for the horizontal acquisition of murine AKR virogenes by recent horizontal infection of the germ line

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Abstract
Several recent reports have established the biological and molecular genetic similarity between the endogenous AKV virus of strain AKR and an N-ecotropic endogenous virus found in the genome of feral Japanese mice, Mus musculus molossimus. The similarities are so striking as to suggest a common origin of these viruses, which are present in some, but not all, inbred mouse strains. The virogenes of AKR mice may have been acquired by either: common descent of AKR (and other AKV+ strains) from a common ancestor of AKR and M. musculus molossimus animals or horizontal germ line infection of the AKR strains by M. musculus molossimus virus at the strain''s inception followed by fixation through inbreeding. The sexual descent model carries with it a prediction of relative consanguinity of the AKR strain and M. musculus molossimus, the horizontal infection model does not. The polymorphic allozyme (allelic isozyme) genotype of 51 nonvirus-related loci was examined in 17 strains of mice including AKR, C58, BALB/c, Swiss and M. musculus molossimus. By comparing the composite allozyme genotype of different inbred and outbred mouse strains, the genetic distance statistic was derived. Genetic distance measures the degree of allelic substitution between populations and increases proportionately with the amount of time the populations were reproductively isolated. The genetic distance computed between M.musculus molossimus and AKR is large, .apprx. 5-10 times the distance between known related populations and strains (C57L vs. C57BL/6). M. musculus molossimus had a similarly large distance from AKV negative strains (Swiss, C57L) as it did from AKV-positive strains. Cellular DNA sequences that flank the integrated AKV provirus were analyzed by restriction enzyme digestion of liver DNA from M. musculus molossimus, AKR and additional inbred strains that express ecotropic murine leukemia virus. The integration flanks of 3 AKR provirus sequences, Akv-1, Akv-2 and a 3rd uncharacterized sequence, were not evident in M. musculus molossimus cell DNA, which contained at least 6 different proviral integration fragments. These data effectively exclude the interpretation of consanguinity of AKR and M. musculus molossimus and support the notion of acquisition of the endogenous virus in AKR by horizontal infection of the M. musculus molossimus virus.