SEQUENCE OF THE CANINE HERPESVIRUS THYMIDINE KINASE GENE - TAXON-PREFERRED AMINO-ACID-RESIDUES IN THE ALPHAHERPESVIRAL THYMIDINE KINASES

Multiple sequence alignments of evolutionarily related proteins are fi nding increasing use as indicators of critical amino acid residues nec essary for structural stability or involved in functional domains resp onsible for catalytic activities. In the past, a number of alignments have provided such information for the herpesviral thymidine kinases, for which three-dimensional structures are not yet available. We have sequenced the thymidine kinase gene of a canine herpesvirus, and with a multiple alignment have identified amino acids preferentially conser ved in either of two taxons, the genera Varicellovirus and Simplexviru s, of the subfamily Alphaherpesvirinae. Since some regions of the thym idine kinases show otherwise elevated levels of substitutional toleran ce, these conserved amino acids are candidates for critical residues w hich have become fixed through selection during the evolutionary diver gence of these enzymes. Several pairs with distinctive patterns of dis tribution among the various viruses occur in or near highly conserved sequence motifs previously proposed to form the catalytic site, and we speculate that they may represent interacting, co-ordinately variable residues.