Evolution of the dUTPase Gene of Mammalian and Avian Herpesviruses

Authors: McGeehan J.E.; Depledge N.W.; McGeoch D.J.

Source: Current Protein and Peptide Science, Volume 2, Number 4, December 2001 , pp. 325-333(10)

Publisher: Bentham Science Publishers

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Abstract:

Sequences of dUTPases encoded by Alpha- and Gamma herpesviruses resemble other dUTPases in their possession of five conserved motifs, but differ in having greater chain lengths (about twice as long) and in the location of Motif 3 at an N-terminal location relative to the other motifs. It was proposed that the herpesvirus gene arose by intragenic duplication of a standard dUTPase coding sequence and subsequent loss of one copy of each motif from the double-length chain, and that the resulting enzyme was active as a monomer. With knowledge of the trimeric 3D structure of standard dUTPases, it is possible to suggest transformations that occurred in evolutionary development of the herpesvirus dUTPase. The distinct location of Motif 3 can indeed be seen to be consistent with it contributing to a single intramolecular active site with the other motifs. Separately, the occurrence in herpesvirus dUTPases of around 20 to 40 additional residues between Motifs 4 and 5 allows the C-terminal Motif 5 to reach the active site intramolecularly. The driving force behind these evolutionary changes remains obscure. We speculate that they may have allowed acquisition of a novel, presently unknown function by the protein. Consistent with this idea is the observation that in Alpha - and Gamma herpesvirus dUTPases the original locus of Motif 3 is occupied by a distinct conserved sequence (Motif 6) perhaps this element constitutes part of a separate functional capability. Notably, the apparently orthologous protein in Betaherpesviruses lacks the standard motifs while Motif 6 is still present.

Keywords: dUTPase Gene; Gammaherpesvirus

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389203013380964

Publication date: 2001-12-01