The Boltzmann distributions of molecular structures predict likely changes through random mutations.

Area of Science:

• Molecular evolution
• Biophysics
• Computational biology

Background:

• Molecular structures evolve through mutations, connecting genotypes to phenotypes.
• The probability of a mutation yielding a new structure varies significantly, impacting evolutionary outcomes.
• Understanding phenotypic mutation probabilities (φqp) is crucial for modeling molecular evolution.

Purpose of the Study:

• To investigate the biophysical principles governing phenotypic mutation probabilities (φqp).
• To explain and predict how the likelihood of a mutation changing structure p to structure q depends on the target structure q.
• To generalize the concept of plastogenetic congruence to entire neutral spaces of structures.

Main Methods:

• Analysis of genotype-phenotype maps for RNA secondary structures and the HP protein model.
• Focus on phenotypic mutation probabilities (φqp), the likelihood of a random mutation changing structure p to structure q.
• Examination of the relationship between φqp and the Boltzmann frequency of alternative structures.

Main Results:

• A simple biophysical principle explains and predicts φqp based on the target structure q.
• High φqp occurs when sequences folding to structure p are likely to also fold to structure q with high Boltzmann frequency.
• This principle generalizes plastogenetic congruence from individual sequences to neutral spaces of structures.

Conclusions:

• Phenotypic mutation probabilities are predictable via a simple biophysical principle.
• The likelihood of structural changes depends on the prevalence of alternative structures with high Boltzmann frequency.
• Findings offer insights into evolutionary pathways and may aid in estimating mutation likelihoods.