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Comparative Study
, 74 (15), 7079-84

A Hypothesis for DNA Viruses as the Origin of Eukaryotic Replication Proteins

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Comparative Study

A Hypothesis for DNA Viruses as the Origin of Eukaryotic Replication Proteins

L P Villarreal et al. J Virol.

Abstract

The eukaryotic replicative DNA polymerases are similar to those of large DNA viruses of eukaryotic and bacterial T4 phages but not to those of eubacteria. We develop and examine the hypothesis that DNA virus replication proteins gave rise to those of eukaryotes during evolution. We chose the DNA polymerase from phycodnavirus (which infects microalgae) as the basis of this analysis, as it represents a virus of a primitive eukaryote. We show that it has significant similarity with replicative DNA polymerases of eukaryotes and certain of their large DNA viruses. Sequence alignment confirms this similarity and establishes the presence of highly conserved domains in the polymerase amino terminus. Subsequent reconstruction of a phylogenetic tree indicates that these algal viral DNA polymerases are near the root of the clade containing all eukaryotic DNA polymerase delta members but that this clade does not contain the polymerases of other DNA viruses. We consider arguments for the polarity of this relationship and present the hypothesis that the replication genes of DNA viruses gave rise to those of eukaryotes and not the reverse direction.

Figures

FIG. 1
FIG. 1
Amino acid alignment of four highly conserved DNA Pol protein regions. Taxon names are color coded according to clade as in Fig. 3 and are labeled A0 to L5 according to the branch tips therein. Gaps inserted to improve the alignment are indicated by a dash (—). Amino acids are color coded according to side group properties using the following scheme: red, negatively charged (D or E); orange, positively charged (H, K, or R); light green, amide (N or Q); blue, alcohol (S or T); purple, aliphatic (L, I, or V); gray, aromatic (F, Y, or W); brown, small (A or G); dark green, sulfur-containing (M or C); white, proline (P). Abbreviations: Hu, human; VZV, varicella-zoster virus; HSV, herpes simplex virus; cytomeg., cytomegalovirus; HHV, human herpesvirus.
FIG. 2
FIG. 2
Protein map indicating proportional lengths of DNA Pol (black lines) and relative locations of the four conserved Pol protein domains (labeled I to IV). Proteins are mostly “centered” so that region II is aligned.
FIG. 3
FIG. 3
Unrooted neighbor-joining phylogeny based on amino-terminal portion of DNA Pol protein sequences as discussed in the text. Labels at branch tips represent taxa as presented in Fig. 1. Numbers at branch nodes indicate percent bootstrap support for that node based on 500 replications.

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