The mechanism of DNA replication is one of the driving forces of genome 
evolution. Bacterial DNA polymerase III, the primary complex of DNA replication, 
consists of PolC and DnaE. PolC is conserved in Gram-positive bacteria, 
especially in the Firmicutes with low GC content, whereas DnaE is widely 
conserved in most Gram-negative and Gram-positive bacteria. PolC contains two 
domains, the 3'-5'exonuclease domain and the polymerase domain, while DnaE only 
possesses the polymerase domain. Accordingly, DnaE does not have the 
proofreading function; in Escherichia coli, another enzyme DnaQ performs this 
function. In most bacteria, the fidelity of DNA replication is maintained by 
3'-5' exonuclease and a mismatch repair (MMR) system. However, we found that 
most Actinobacteria (a group of Gram-positive bacteria with high GC content) 
appear to have lost the MMR system and chromosomes may be replicated by 
DnaE-type DNA polymerase III with DnaQ-like 3'-5' exonuclease. We tested the 
mutation bias of Bacillus subtilis, which belongs to the Firmicutes and found 
that the wild type strain is AT-biased while the mutS-deletant strain is 
remarkably GC-biased. If we presume that DnaE tends to make mistakes that 
increase GC content, these results can be explained by the mutS deletion (i.e., 
deletion of the MMR system). Thus, we propose that GC content is regulated by 
DNA polymerase and MMR system, and the absence of polC genes, which participate 
in the MMR system, may be the reason for the increase of GC content in 
Gram-positive bacteria such as Actinobacteria.