Phylogenomic Analysis of the Uracil-DNA Glycosylase Superfamily

The spontaneous deamination of cytosine produces uracil mispaired with guanine in DNA, which will produce a mutation, unless repaired. In all domains of life, uracil-DNA glycosylases (UDGs) are responsible for the elimination of uracil from DNA. Thus, UDGs contribute to the integrity of the genetic information and their loss results in mutator phenotypes. We are interested in understanding the role of UDG genes in the evolutionary variation of the rate and the spectrum of spontaneous mutations. To this end, we determined the presence or absence of the five main UDG families in more than 1,000 completely sequenced genomes and analyzed their patterns of gene loss and gain in eubacterial lineages. We observe nonindependent patterns of gene loss and gain between UDG families in Eubacteria, suggesting extensive functional overlap in an evolutionary timescale. Given that UDGs prevent transitions at G:C sites, we expected the loss of UDG genes to bias the mutational spectrum toward a lower equilibrium G + C content. To test this hypothesis, we used phylogenetically independent contrasts to compare the G + C content at intergenic and 4-fold redundant sites between lineages where UDG genes have been lost and their sister clades. None of the main UDG families present in Eubacteria was associated with a higher G + C content at intergenic or 4-fold redundant sites. We discuss the reasons of this negative result and report several features of the evolution of the UDG superfamily with implications for their functional study. uracil-DNA glycosylase, mutation rate evolution, mutational bias, GC content, DNA repair, mutator gene.