Novel class of mouse mammary tumor virus-related DNA sequences found in all species of Mus, including mice lacking the virus proviral genome.

Mice in breeding colonies of feral Mus musculus brevirostris (Azrou, Morocco), M. m. musculus (Studenec, Czechoslovakia), and M. m. molossinus (Fukuoka, Japan) were found to lack the mouse mammary tumor virus (MMTV-alpha) proviral genome in their germ line. MMTV-alpha proviral genomes have been found in all inbred strains of M. musculus by using high-stringency nucleic acid hybridization conditions. We conclude that feral mice in these colonies are heterozygous for a limited number of MMTV-alpha proviral genomes and that those lacking them arose as a result of random chromosomal segregation. All mice in another breeding colony of feral M. m. musculus (Sladeckovce, Czechoslovakia) lack MMTV proviral genes. By relaxing the conditions of nucleic acid hybridization, MMTV-related sequences (designated MMTV-beta) were detected in restricted cellular DNA from MMTV-negative mice and all other inbred strains and feral species of the genus Mus. The apparent ubiquity of the MMTV-beta DNA sequences in the genus Mus and the lack of variation in the pattern of restriction fragments containing these sequences within a species distinguishes them from MMTV-alpha. These results suggest that the MMTV-beta DNA sequences either are the evolutionary progenitors of the infectious MMTV genome or represent an accumulation of evolutionarily divergent MMTV-alpha insertions into the mouse germ line.