Several mechanisms that increase the rate of mutagenesis across the entire 
genome have been identified; however, how the rate of evolution might be 
promoted in individual genes is unclear. Most genes in bacteria are encoded on 
the leading strand of replication. This presumably avoids the potentially 
detrimental head-on collisions that occur between the replication and 
transcription machineries when genes are encoded on the lagging strand. Here we 
identify the ubiquitous (core) genes in Bacillus subtilis and determine that 17% 
of them are on the lagging strand. We find a higher rate of point mutations in 
the core genes on the lagging strand compared with those on the leading strand, 
with this difference being primarily in the amino-acid-changing (nonsynonymous) 
mutations. We determine that, overall, the genes under strong negative selection 
against amino-acid-changing mutations tend to be on the leading strand, 
co-oriented with replication. In contrast, on the basis of the rate of 
convergent mutations, genes under positive selection for amino-acid-changing 
mutations are more commonly found on the lagging strand, indicating faster 
adaptive evolution in many genes in the head-on orientation. Increased gene 
length and gene expression amounts are positively correlated with the rate of 
accumulation of nonsynonymous mutations in the head-on genes, suggesting that 
the conflict between replication and transcription could be a driving force 
behind these mutations. Indeed, using reversion assays, we show that the 
difference in the rate of mutagenesis of genes in the two orientations is 
transcription dependent. Altogether, our findings indicate that head-on 
replication-transcription conflicts are more mutagenic than co-directional 
conflicts and that these encounters can significantly increase adaptive 
structural variation in the coded proteins. We propose that bacteria, and 
potentially other organisms, promote faster evolution of specific genes through 
orientation-dependent encounters between DNA replication and transcription.