Clusters of orthologous groups [COGs; Tatusov, R. L., Koonin, E. V. & Lipma
n, D. J. (1997) Science 278, 631-637] were identified for a set of 13 compl
etely sequenced herpesviruses. Each COG represented a family of gene produc
ts conserved across several herpes genomes. These families were defined wit
hout using an arbitrary threshold criterion based on sequence similarity. T
he COG technique was modified so that variable stringency in COG constructi
on was possible. High stringencies identify a core set of highly conserved
genes. Varying COG stringency reveals differences in the degree of conserva
tion between functional classes of genes. The COG data were used to constru
ct whole-genome phylogenetic trees based on gene content. These trees agree
well with trees based on other methods and are robust when tested by boots
trap analysis. The COG data also were used to construct a reciprocal tree t
hat clustered genes with similar phylogenetic profiles. This clustering may
give clues to genes with related functions or with related histories of ac
quisition and loss during herpesvirus evolution.