The herpesvirus lifestyle results in a long-term interaction between host and invading pathogen, resulting in exquisite adaptation of virus to host. We have sequenced the genomes of nine strains of murine cytomegalovirus (a betaherpesvirus), isolated from free-living mice trapped at locations separated geographically and temporally. Despite this separation these genomes were found to have low levels of nucleotide variation. Of the more than 160 open reading frames, almost 90% had a dN/dS ratio of amino acid substitutions of less than 0.6, indicating the level of purifying selection on the coding potential of MCMV. Examination of selection acting on individual genes at the codon level however indicates some level of positive selection, with 0.03% of codons showing strong evidence for positive selection. Conversely, 1.3% of codons show strong evidence of purifying selection. Alignments of both genome sequences and coding regions suggested that high levels of recombination have shaped the MCMV genome.
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