Lack of self-averaging in neutral evolution of proteins

TL;DR

This study uses simulations of neutral protein evolution under stability constraints to reveal non-Poissonian mutation patterns and correlations, challenging the assumption of self-averaging in evolutionary processes.

Contribution

It demonstrates that neutral evolution of proteins exhibits non-Poissonian and correlated mutation patterns, highlighting the breakdown of self-averaging in such evolutionary trajectories.

Findings

Neutral mutations fluctuate broadly across sequences

Evolutionary substitution process shows strong correlations

Self-averaging does not hold in simulated protein evolution

Abstract

We simulate neutral evolution of proteins imposing conservation of the thermodynamic stability of the native state in the framework of an effective model of folding thermodynamics. This procedure generates evolutionary trajectories in sequence space which share two universal features for all of the examined proteins. First, the number of neutral mutations fluctuates broadly from one sequence to another, leading to a non-Poissonian substitution process. Second, the number of neutral mutations displays strong correlations along the trajectory, thus causing the breakdown of self-averaging of the resulting evolutionary substitution process.