Evolution and degeneration of eukaryotic DNA replication system.

Several molecular forms of DNA polymerases have been identified in eukaryotic cells. Although three DNA polymerases alpha, delta, and epsilon, have been well studied and indicated to be involved in nuclear DNA replication process, it remains unclear how this hetero-polymerase system might have arisen. Here I wish to consider its past and future, viewed in the context of molecular evolution. Comparative analysis has revealed some nucleotides and/or amino acids to be conserved in DNA polymerase delta, in polymerase domains III and IV, which have disappeared in DNA polymerase alpha. Furthermore, the codon usage for serine residues in conserved domains of DNA polymerase alpha varies and is not as conservative as for DNA polymerase delta. Recently and in the present study, I have reported that DNA polymerase delta could substitute for the function of DNA polymerase alpha in vitro, and proposed the hypothesis that eukaryotic DNA polymerase alpha arose due to symbiotic contacts. This 'exogenous' polymerase would be expected to be excluded from the eukaryotic DNA replication system, and my analysis in the present study suggests it is about to degenerate.