Quantitation of the relatedness of reovirus serotypes 1, 2, and 3 at the gene level

As judged by the ability of their genomes to hybridize, reovirus serotypes 1 and 3 are related to the extent of about 70% to each other and about 10% to serotype 2. Two techniques were developed to measure the extent to which the individual cognate genes of these serotypes are related. Both involve comparison of heterologous hybrid genes that contain plus and minus strands of genes of different serotypes with homologous hybrid genes (molecules formed by reannealing the separated plus and minus strands of the same gene). In the first technique, the amounts in such hybrids of material sensitive to ribonuclease under standard conditions were compared; in the second, their relative electrophoretic mobilities. The results obtained with the two techniques agreed well. They showed that for the three reovirus isolates examined (the Lang strain of serotype 1, the D5 Jones strain of serotype 2, and the Dearing strain of serotype 3), all 10 genes of serotypes 1 and 3 are much more closely related to each other than to the genes of serotype 2. Although this result relates to only three isolates of mammalian reovirus, it suggests that the gene sets of reovirus serotypes 1, 2, and 3 evolved independently of each other. Apparently double infection of hosts with strains of two reovirus serotypes, which would very likely yield recombinants, occurs infrequently and/or such recombinants have a lower survival advantage than strains containing “pure” gene sets. The results also show that the gene that has diverged most markedly during evolution is the S1 gene, the gene that encodes the minor outer shell capsid protein σ1 which is the reovirus cell attachment protein and hemagglutinin and possesses the most type-specific antigenic determinants. The serotype 1 and 3 S1 genes are about 10% homologous, serotype 2 and serotype 1 or 3 S1 genes about 3%. The genes that have diverged least are the three L genes (85–90% homology for the serotype 1 and 3 L genes). In all cases, the serotype 2 and serotype 1 or 3 genes exhibit no more than 20%, and often less than 10% homology. In spite of this high degree of divergence, the antigenic determinants on proteins encoded by genes of serotype 2 on the one hand and serotypes 1 and 3 on the other hand are, with the exception of those on proteins σ1, highly conserved, and the 60 to 80 nucleotides at the 5′- and 3′-termini of at least three sets of cognate genes (L3, M3, and S2) of all three serotypes, serotype 1 and 3 as well as serotype 2, are highly homologous and in some instances almost identical. Thus, while some regions of reovirus genes have diverged greatly during evolution, others have been highly conserved.