Molecular evolution of the gamma-Herpesvirinae

Genomic sequences available for members of the gamma-Herpesvirinae allow analysis of many aspects of the group's evolution. This paper examines four topics: (i) the phylogeny of the group; (ii) the histories of gamma-herpesvirus-specific genes; (iii) genomic variation of human herpesvirus 8 (HHV-8); and (iv) the relationship between Epstein-Barr virus types 1 and 2 (EBV-1 and EBV-2). A phylogenetic tree based on eight conserved genes has been constructed for eight gamma-herpesviruses and extended to 14 species with smaller gene sets. This gave a generally robust assignment of evolutionary relationships, with the exception of murine herpesvirus 4 (MHV-4), which could not be placed unambiguously on the tree and which has evidently experienced an unusually high rate of genomic change. The gamma-herpesviruses possess a variable complement of genes with cellular homologues. In the clearest cases these virus genes were shown to have originated from host genome lineages in the distant past. HHV-8 possesses at its left genomic terminus a highly diverse gene (K1) and at its right terminus a gene (K15) having two diverged alleles. It was proposed that the high diversity of K1 results from a positive selection on K1 and a hitchhiking effect that reduces diversity elsewhere in the genome. EBV-1 and EBV-2 differ in their alleles of the EBNA-2, EBNA-3A, EBNA-3B and EBNA-3C genes. It was suggested that EBV-1 and EBV-2 may recombine in mixed infections so that their sequences outside these genes remain homogeneous. Models for genesis of the types, by recombination between diverged parents or by local divergence from a single lineage, both present difficulties.