Toward a comprehensive phylogeny for mammalian and avian herpesviruses

Abstract

With the aim of deriving a definitive phylogenetic tree for as many mammalian and avian herpesvirus species as possible, alignments were made of amino acid sequences from eight conserved and ubiquitously present genes of herpesviruses, with 48 virus species each represented by at least one gene. Phylogenetic trees for both single-gene and concatenated alignments were evaluated thoroughly by maximum-likelihood methods, with each of the three herpesvirus subfamilies (the Alpha-, Beta-, and Gammaherpesvirinae) examined independently. Composite trees were constructed starting with the top-scoring tree based on the broadest set of genes and supplemented by addition of virus species from trees based on narrower gene sets, to give finally a 46-species tree; branching order for three regions within the tree remained unresolved. Sublineages of the Alpha- and Betaherpesvirinae showed extensive cospeciation with host lineages by criteria of congruence in branching patterns and consistency in extent of divergence. The Gammaherpesvirinae presented a more complex picture, with both higher and lower substitution rates in different sublineages. The final tree obtained represents the most detailed view to date of phylogenetic relationships in any family of large-genome viruses.

FIG. 1

Flow diagram for creation of composite trees. The box at top left indicates the starting maximum-likelihood tree based on the eight-gene alignment; the other boxes represent trees that contributed to building composite trees. Successive composite MC trees are shown as circles with numbers of species added from different data sets shown above arrows; the final 46-species multifurcated tree is shown at bottom right.

FIG. 2

The 20-species phylogenetic trees. (A) Unconstrained maximum-likelihood tree obtained using Codeml and with alignment sites in eight rate classes. The tree is shown in a rooted format as specified in Materials and Methods, and the mean position of branch tips is indicated by the dashed line. (B) Equivalent rooted MC tree. Divergence scale (substitutions/site) for both is at the bottom.

FIG. 3

The 28-species phylogenetic tree. The unconstrained maximum-likelihood tree from the UL27-plus-UL30 alignment is shown as for Fig. 1A, with species contributed to the 28-species composite tree marked with circles.

FIG. 4

The 46-species composite trees. (A) The 46-species composite MC tree. (B) Subfamily portions of the same tree with regions of uncertain branching drawn as multifurcations (heavy lines). Subfamily and sublineage designations are at the right.

FIG. 5

Comparison between divergences for branch points in the herpesvirus tree and dates of corresponding events in mammalian evolution. The graph compares divergence values (substitutions/site in one lineage) for features in the composite tree (Fig. 4) with dates of possible equivalents in host evolution (10) in millions of years before the present (My). Filled symbols, data from 20-species MC tree; open symbols, data from 46-species tree; squares, α2 sublineage; triangles, β1 sublineage. The line was drawn through the origin and the four highest-value filled symbols. Divergence events and times for filled symbols: humans/chimpanzees, 5.5 My; suidae/ruminants, 64.7 My; artiodactyls/perissodactyls, 83.4 My; primates/ungulates, 92.0 My; primates/rodents, (sciurognathi), 112 My. Similarly for open symbols: human/cercopithecidae, 23.3 My; mice/rats, 40.7 My; feliformia/caniformia, 46.2 My; carnivores/perissodactyls, 74.0 My. Dates in reference included error estimates.