The consequences of base pair composition biases for regulatory network organization in prokaryotes

Given the dramatic variation in guanine-cytosine (GC) content observed in prokaryotes, from approximately 20% to approximately 75% GC, one wonders if these extreme biases in base pair composition affect the evolution of transcription factor-binding sites (BS). This letter shows that, along the wide range of GC content variation in bacteria, bacterial BS keep a high frequency of AT bases, roughly independently of the background (BG) base pair composition of intergenic regions. As a result, the equilibrium base pair frequencies of BS depart the most from those of BS DNA in GC-rich genomes. This not only implies a higher specificity but also a higher coding barrier for BS in GC-rich genomes. In accordance, we observe that the average percentage of divergently transcribed regions increases with the GC content of the genome, suggesting the use of a more efficient coding strategy.