The sequences of the reovirus serotype 1, 2, and 3 L1 genome segments and analysis of the mode of divergence of the reovirus serotypes.

We report the sequence of the L1 genome segment of reovirus serotype 3 strain Dearing, which encodes the minor core component protein lambda 3. It is 3854 bp long, with a long open reading frame starting at position 19 that is 1267 codons long. Protein lambda 3 is not detectably related to any other protein, nor does it appear to possess motifs indicative of recognized specialized functions. We have also sequenced the L1 genome segments of reovirus serotypes 1 and 2. The serotype 1 and 3 L1 genome segments are extremely closely related; there are only 154 mismatches (4.1%), 80% of which are in third base codon positions, so that these two lambda 3 proteins are 98.3% related (only 22 mismatches out of 1267). The serotype 2 L1 genome segment is only 75% related to the serotype 1 and 3 genome segments, and the serotype 2 lambda 3 protein is 92% related to the serotype 1 and 3 lambda 3 proteins. We have also analyzed the divergence patterns by which the various reovirus genome segments evolved into the three serotype forms. It appears that serotype 2 separated from the serotype 1/3 precursor long before serotypes 1 and 3 themselves diverged. In all cases the third base codon positions in the various genome segments have diverged about 80% toward randomness. The first and second base codon positions have diverged much less and to varying degree, depending, presumably, on each protein's ability to accept changes without significant loss of function. For the separation into the serotype 1 and 3 forms, the extent of divergence of the various genome varies over a very wide range. The S1 genome segments have again diverged most extensively, the extent of divergence in the first, second, and third base codon positions being about 50, 35 and 75%, respectively. For seven other genome segments that we examined the extent of third base codon position divergence is 56, 53, 48, 29, 22, 13, and 6%, whereas first and second base codon position divergence ranges from no more than 6 to 2 and 3 to less than 1%, respectively. The most likely explanation of these patterns is that the separation of the various genome segments into the present-day serotype 1 and 3 associated forms occurred at different times during evolution, from progenitors that were genome segment reassortants with survival rates as high as or higher than those of homologous genome segment sets.