Adaptation through stochastic switching into transient mutators in finite asexual populations

TL;DR

This study models how asexual populations adapt through transient mutator states, revealing a universal pathway involving stochastic switching, hitchhiking mutations, and subsequent reversion, driven by biophysical principles.

Contribution

It introduces a microscopic biophysical model showing that adaptation involves a transient mutator phase with a specific sequence of genetic events.

Findings

Adaptation involves transient mutator fixation regardless of fitness landscape perturbations.

The pathway includes stochastic switching, hitchhiking mutations, and reversion to non-mutator.

Results suggest universal physical principles underlying evolutionary adaptation.

Abstract

The importance of mutator clones in the adaptive evolution of asexual populations is not fully understood. Here we address this problem by using an ab initio microscopic model of living cells, whose fitness is derived directly from their genomes using a biophysically realistic model of protein folding and interactions in the cytoplasm. The model organisms contain replication controlling genes (DCGs) and genes modeling the mismatch repair (MMR) complexes. We find that adaptation occurs through the transient fixation of a mutator phenotype, regardless of particular perturbations in the fitness landscape. The microscopic pathway of adaptation follows a well-defined set of events: stochastic switching to the mutator phenotype first, then mutation in the MMR complex that hitchhikes with a beneficial mutation in the DCGs, and finally a compensating mutation in the MMR complex returning the population to a non-mutator phenotype. Similarity of these results to reported adaptation events points out to robust universal physical principles of evolutionary adaptation.