Thermodynamic perspectives into DNA stability and information encoding in the human genome

The perpetuation of species depends on two critical factors at the DNA level: the encoding of information essential for survival and adaptation, and the stability of DNA to preserve this information. Focusing on the latter, this study posits and confirms that local interactions within DNA are sufficient to explain the observed Chargaff’s symmetries, providing a thermodynamic foundation for genome stability. Our analyses show that encoding genetic information incurs an energetic cost, with an effective energy expenditure of approximately one-tenth of kT per base when comparing exonic sequences to intronic and intergenic regions. Furthermore, pathogenic mutations tend to drive segments toward lower effective energy states, with pronounced effects observed in disease-associated mutations. By evaluating the effective energy of DNA sequences, this framework offers valuable insights into the interplay between physical principles, information encoding, and mutation dynamics.