MOLECULAR EVOLUTION OF HERPESVIRUSES - GENOMIC AND PROTEIN-SEQUENCE COMPARISONS

Phylogenetic reconstruction of herpesvirus evolution is generally foun ded on amino acid sequence comparisons of specific proteins. These are relevant to the evolution of the specific gene (or set of genes), but the resulting phylogeny may vary depending on the particular sequence chosen for analysis (or comparison). In the first part of this report , we compare 13 herpesvirus genomes by using a new multidimensional me thodology based on distance measures and partial orderings of dinucleo tide relative abundances. The sequences were analyzed with respect to (i) genomic compositional extremes; (ii) total distances within and be tween genomes; (iii) partial orderings among genomes relative to a set of sequence standards; (iv) concordance correlations of genome distan ces; and (v) consistency with the alpha-, beta-, gammaherpesvirus clas sification. Distance assessments within individual herpesvirus genomes show each to be quite homogeneous relative to the comparisons between genomes. The gammaherpesviruses, Epstein-Barr virus (EBV), herpesviru s saimiri, and bovine herpesvirus 4 are both diverse and separate from other herpesvirus classes, whereas alpha- and betaherpesviruses overl ap. The analysis revealed that the most central genome (closest to a c onsensus herpesvirus genome and most individual herpesvirus sequences of different classes) is that of human herpesvirus 6, suggesting that this genome is closest to a progenitor herpesvirus. The shorter DNA di stances among alphaherpesviruses supports the hypothesis that the alph a class is of relatively recent ancestry. In our collection, equine he rpesvirus 1 (EHV1) stands out as the most central alphaherpesvirus, su ggesting it may approximate an ancestral alphaherpesvirus. Among all h erpesviruses, the EBV genome is closest to human sequences. In the DNA partial orderings, the chicken sequence collection is invariably as c lose as or closer to all herpesvirus sequences than the human sequence collection is, which may imply that the chicken (or other avian speci es) is a more natural or more ancient host of herpesviruses. In the se cond part of this report, evolutionary relationships among the 13 herp esvirus genomes are evaluated on the basis of recent methods of amino acid alignment applied to four essential protein sequences. In this an alysis, the alignment of the two betaherpesviruses (human cytomegalovi rus versus human herpesvirus 6) shelved lower scores compared with ali gnments within alphaherpesviruses (i.e., among EHV1, herpes simplex vi rus type 1, varicella-zoster virus, pseudorabies virus type 1 and Mare k's disease virus) and within gammaherpesviruses (EBV versus herpesvir us saimiri). Comparisons within the alpha class generally produced the highest alignment scores, with EHV1 and pseudorabies type 1 prominent , whereas herpes simplex virus type 1 versus varicella-zoster virus sh ow the least similarity among the alpha sequences. The within-alpha, b eta, and gamma class sequence similarity scores are generally 50 to 10 0% higher than the between-class sequence similarity scores. These res ults suggest that the betaherpesviruses separated earlier than the for mation of the gamma class and that the alpha class may be of the most recent ancestry. By our methods, evolutionary relationships derived fr om genomic comparisons versus protein comparisons differ to some exten t. The dinucleotide relative abundance distances appear to discriminat e DNA structure specificity more than sequence specificity. The evolut ionary development of genes among viruses (and species) is more depend ent on each individual gene.