%0 Journal Article %T On the molecular mechanism of GC content variation among eubacterial genomes %A Hao Wu %A Zhang Zhang %A Songnian Hu %A Jun Yu %J Biology Direct %D 2012 %I BioMed Central %R 10.1186/1745-6150-7-2 %X Mutator genes, especially those with dominant effects on the mutation spectra, are biased towards either GC or AT richness, and they alter genomic GC content in the two opposite directions. Increased bacterial genome size (or gene number) appears to rely on increased genomic GC content; however, it is unclear whether the changes are directly related to certain environmental pressures. Certain environmental and bacteriological features are related to GC content variation, but their trends are more obvious when analyzed under the dnaE-based grouping scheme. Most terrestrial, plant-associated, and nitrogen-fixing bacteria are members of the dnaE1|dnaE2 group, whereas most pathogenic or symbiotic bacteria in insects, and those dwelling in aquatic environments, are largely members of the dnaE1|polV group.Our studies provide several lines of evidence indicating that DNA polymerase III ¦Á subunit and its isoforms participating in either replication (such as polC) or SOS mutagenesis/translesion synthesis (such as dnaE2), play dominant roles in determining GC variability. Other environmental or bacteriological factors, such as genome size, temperature, oxygen requirement, and habitat, either play subsidiary roles or rely indirectly on different mutator genes to fine-tune the GC content. These results provide a comprehensive insight into mechanisms of GC content variation and the robustness of eubacterial genomes in adapting their ever-changing environments over billions of years.This paper was reviewed by Nicolas Galtier, Adam Eyre-Walker, and Eugene Koonin.As one of the key parameters of genome sequences, the genomic GC content, confined to between 25% and 75%, has been investigated for over half a century [1-3]. There are several essential questions to be addressed concerning GC content and its variability. First, how does it vary: randomly, gene-centrically, species-specifically, regulated, or selected? Second, at what level does GC content vary: replication, transcription %U http://www.biology-direct.com/content/7/1/2