Molecular cloning and sequencing of the gene (M2) encoding the major virion structural protein (mu 1-mu 1C) of serotypes 1 and 3 of mammalian reovirus.
Full-length c-DNA copies of the M2 gene from the Lang strain of type 1 and the Dearing strain of type 3 reovirus have been cloned in the Escherichia coli plasmid pAT153. DNA sequencing of these clones showed that the type 3 gene was 2207 nucleotides long and the single long open reading frame encoded a primary translation product (mu 1) of 709 amino acids with a molecular weight of 76,000. The type 1 gene was three nucleotides shorter at 2204 with the deletions occurring near the center of the coding sequence so that the primary translation product of this gene was one amino acid shorter at 708. Sequence homology between the two genes had an overall value of 85%, rising to 95% when only the noncoding sequences were compared. The 334 nucleotide changes between the two genes were distributed throughout the sequence with no apparent areas of concentration. Comparison of the predicted amino acid sequences showed that there were 24 differences between the two giving a homology of 96.6% at the protein level. The amino acid changes of which only 9 were nonconservative were again spread fairly evenly throughout the coding sequence although there was one small patch of 5 changes in a stretch of 10 amino acids near the carboxyl terminus. The post-translational cleavage to convert mu 1 to the major virion protein mu 1C is revealed as involving the removal of 42 amino acids exclusively from the amino terminus of mu 1. Simple addition of trypsin-sensitive cleavage sites or predicted secondary structure failed to show the cause of the large difference known to exist in the protease sensitivities of virions carrying these two proteins.