Evolution of herpesvirus thymidine kinases from cellular deoxycytidine kinase

Abstract

The thymidine kinases encoded by herpesviruses of higher vertebrates form a distinct group and are unrelated to the thymidine kinases (TKs) of other organisms. Their evolutionary source has not been identified, but our analysis has revealed a clear relationship with a sequence of human deoxycytidine kinase (dCK) published recently. We report the sequence of the putative TK of channel catfish virus, a herpesvirus of a lower vertebrate, and show that it is also related to dCK. We propose, therefore, that the TKs of herpesviruses of higher and lower vertebrates have evolved, either independently or successively, from a cellular dCK.

Cloning and expression of human mitochondrial deoxyguanosine kinase cDNA

“…The similarity in the deduced protein sequence were overall 46% and in some regions as high as 70%. Two Bacillus subtilis proteins (25.4 and 24.1 kDa, respectively) [20], one Fowl pox virus 25.9 kDa polypeptide [21] as well as a ictalurid herpes virus 1 [22] and a saimiriine herpes virus 1 thymidine kinase [23] are all part of a group of sequences that show considerably lower but still significant similarities to human dGK. The only other dGK protein sequence present in the GenBank is that of Lactobacillus acidophilus [24].…”

“…Basic amino acids presumably involved in mitochondrial localization signal for dGK are underlined. Residues marked with * indicates regions of conservation with other members of the deoxynucleoside kinases [18][19][20][21][22][23][24][25][26][27].…”

Herpesviral thymidine kinases: laxity and resistance by design.

“…Since HSV-CAIJ 1 TK and certain other viral TK molecules can phosphorylate deoxycytidine in addition to thymidine, attention has been drawn to the fact that the channel catfish herpesviral TK bears about as much sequence homology to human cellular deoxycytidine kinase as to HSV-1 TK (Harrison et al, 1991). Similar sequence homologies have been found between HSV-1 TK and human mitochondrial deoxyguanosine kinase, which has recently been cloned and expressed (Johansson & Karlsson, 1996).…”

Kinetic studies of the predicted substrate-binding site of varicella-zoster virus thymidine kinase

“…However, the optimum distance between the VZV TK ATP-and substrate-binding sites was the same as for cellular TK and was shorter than that of cellular TM-K by a length equivalent to one phosphate group (Davies et al, 1988). Robertson & Whalley (1988) and Smith et al (1989) suggested that the origin of herpesvirus TKs may be a host cell TM-K and recently Harrison et al (1991) suggested that herpesvirus TKs have evolved from a captured cellular dCK gene. Analyses of the distance between the ATP-and substrate-binding sites of cellular kinases may aid the understanding of which kinase is the origin of the enzymes.…”

“…Previous studies of the sequences of herpesvirus TKs showed various degrees of similarity between them, demonstrated their evolution and divergence, and aroused interest in the relationship between their structure and function (Gentry et al, 1983;Honess et al, 1989;Harrison et al, 1991).…”