MBE Advance Access published online on June 27, 2003
Molecular Biology and Evolution, doi:10.1093/molbev/msg177
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2003; all rights reserved
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1 Department of Biology, Indiana University, Bloomington, IN 47405, USA
* To whom correspondence should be addressed. E-mail: ddenver{at}bio.indiana.edu.
The helix-hairpin-helix superfamily of base excision repair DNA glycosylases is composed of multiple phylogenetically diverse enzymes that are capable of excising varying spectra of oxidatively and methyl-damaged bases. Although these DNA repair glycosylases have been widely studied through genetic, biochemical, and biophysical approaches, the evolutionary relationships of different helix-hairpin-helix homologues and the extent to which they are conserved across phylogeny remain enigmatic. We provide an evolutionary framework for this pervasive and versatile superfamily of DNA glycosylases. Six helix-hairpin-helix gene families (named AlkA, MpgII, MutY/Mig, Nth, OggI, and OggII) are identified through phylogenetic analysis of 234 homologues found in 94 genomes (16 archaea, 64 bacteria, and 14 eukaryotes). The number of homologues in each gene family varies from 117 in the Nth family (nearly every genome surveyed harbors at least one Nth homologue) to only five in the divergent OggII family (all from archaeal genomes). Sequences from all three domains of life are included in four of the six gene families, suggesting that the HhH superfamily diversified very early in evolution. The phylogeny provides evidence for multiple lineage-specific gene duplication events, most of which involve eukaryotic homologues in the Nth and AlkA gene families. We observe extensive variation in the number of helix-hairpin-helix superfamily glycosylase genes present in different genomes, possibly reflecting major differences among species in the mechanisms and pathways by which damaged bases are repaired and/or disparities in the basic rates and spectra of mutation experienced by different genomes. Key Words:
Base excision repair, Gene duplication, Genome, Glycosylase, Helix-hairpin-helix, Phylogenetic analysis
© 2003 Society for Molecular Biology and Evolution
Original Articles
An Evolutionary Analysis of the Helix-Hairpin-Helix Superfamily of DNA Repair Glycosylases
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