Evolutionary Advantage of Diversity-Generating Retroelements in Switching Environments

TL;DR

This paper develops a theoretical framework to understand how Diversity-Generating Retroelements (DGRs) provide evolutionary advantages in fluctuating environments by enabling rapid genetic variation, especially in microbial genomes.

Contribution

It introduces a two-timescale analytical model to explain the conditions favoring DGR activity and its evolutionary maintenance in switching environments.

Findings

DGRs confer fitness benefits during environmental changes.

Constitutive DGR activation is evolutionarily advantageous under certain conditions.

The model aligns with observed DGR activity in human gut bacteria.

Abstract

Diversity-Generating Retroelements (DGRs) create rapid, targeted variation within specific genomic regions in phages and bacteria. They operate through stochastic retro-transcription of a template region (TR) into a variable region (VR), which typically encodes ligand-binding proteins. Despite their prevalence, the evolutionary conditions that maintain such hypermutating systems remain unclear. Here we introduce a two-timescale framework separating fast VR diversification from slow TR evolution, allowing the dynamics of DGR-controlled loci to be analytically understood from the TR design point of view. We quantity the fitness gain provided by the diversification mechanism of DGR in the presence of environmental switching with respect to standard mutagenesis. Our framework accounts for observed patterns of DGR activity in human-gut \textit{Bacteroides} and clarifies when constitutive DGR activation is evolutionarily favored.