Molecular evolution of murine cytomegalovirus genomes

Cytomegaloviruses have co-evolved with their hosts since the mammalian radiation. The MCMV genome appears to be highly conserved and unlike the HCMV genome contains no large-scale deletions and rearrangements following serial in-vitro passage. The genome of MCMV is both highly conserved and highly variable. The central regions of the genome, containing the betaherpesvirus and herpesvirus conserved genes, are highly conserved. However, significant variation occurs in species-specific genes at genomic termini, where the know and putative immune evasion genes reside. Variation in the MCMV genome consists of presence/absence polymorphisms in individual genes, grouping of genes into specific genotypes and random nucleotide diversity across the genome. However, much of the genotypic variation is under strong purifying selection indicating that these genotypes are fixed and conserved at the population level. The individual genotypes are either known to, or are likely to, target variant host gene products. Consequently, in vivo replication of MCMV is likely to be viral strain dependent and reflect the particular repertoire of genes encoded by the infecting strain. A total of 22 MCMV genes are genotypic, indicating considerable potential for variation in the MCMV population. This variation likely reflects genetic heterogeneity in the target population and suggests exquisite adaptation of the virus to its host.