Evolutionary pattern of four representative DNA repair proteins across six model organisms: an in silico analysis

Abstract

DNA repair refers to a collection of processes by which a cell identifies and corrects damage to DNA molecules that encodes its genome. In this study, we examined evolution of O6-Methylguanine DNA alkyltransferase (MGMT), Xeroderma pigmentosum group D (XPD) protein, G/T mismatch-specific DNA glycosylases, MutS DNA repair proteins of Escherichia coli, Pyrococcus kodakaraensis, Saccharomyces cerevisae, Drosophila melanogester, Mus musculus, and Homo sapiens, which are involved in direct repair, Nucleotide excision repair, base excision repair, and mismatch repair, respectively. Sequence and domain analysis of these proteins indicates that during the course of evolution catalytic residues in the catalytic domain remain conserved. Phylogenetic tree analysis suggested that MGMT proteins of human and mouse have archaeal origin, whereas XPD proteins which are responsible for nucleotide excision repair evolved progressively from lower organism to higher organism. G/T mismatch-specific DNA glycosylases belong to family 1, family 2, and family 4 of uracil-DNA glycosylases superfamily. Family 2 proteins have broader substrate specificity in comparison to proteins of other families. In eukaryotic organisms, prokaryotic MUTS genes are duplicated and various paralogs are present. No unified evolution mechanism can explain the evolution of all these DNA repair proteins. Large sequence variation is observed among same DNA repair proteins of different organisms. However, residues involved DNA repair work and DNA binding remain conserved during the course of evolution.