DNA thermodynamic pressure: a potential contributor to genome evolution.

Codon usage bias is a feature of living organisms. The origin of this bias might be explained not only by external factors but also by the nature of the structure of deoxyribonucleic acid (DNA) itself. We have developed a point mutation simulation program of coding sequences, in which nucleotide replacement follows thermodynamic criteria. For this purpose we calculated the hydrogen bond-like and electrostatic energies of non-canonical base pairs in a 5 bp neighbourhood. Although the rate of non-canonical base pair formation is extremely low, such pairs occur with a preference towards a guanine (G) or cytosine (C) rather than an adenine (A) or thymine (T) replacement due to thermodynamic considerations. This feature, according to the simulation program, should result in an increase in the GC content of the genome over evolutionary time. In addition, codon bias towards a higher GC usage is also predicted. DNA sequence analysis of genes of the Trypanosomatidae lineage supported the hypothesis that DNA thermodynamic pressure is a driving force that impels increases in GC content and GC codon bias.