Background: Acceleration of adaptation dynamics by stress-induced hypermutation has been found experimentally. Evolved evolvability is a prominent explanation. We investigate a more generally applicable explanation by a physical constraint.

Methods and Results: A generic thermodynamical analysis of genetic information storage obviates physical constraints on the integrity of genetic information. The capability to employ metabolic resources is found as a major determinant of mutation probability in stored genetic information. Incorporation into a non-recombinant, asexual adaptation toy model redicts cases of markedly accelerated adaptation, driven by a transient increase of mutation rate. No change in the mutation rate as a genetic trait is required. The mutation rate of one and the same genotype varies dependent on stress level.

Implications: Stress-dependent mutation rates are physically necessary and challenge a condition-independent genotype to mutation rate mapping. This holds implications for evolutionary theory and pathogen and cancer evolution.