Evolutionary Repair Experiments as a Window to the Molecular Diversity of Life

Abstract

Comparative genomics reveals an unexpected diversity in the molecular mechanisms underlying conserved cellular functions, such as DNA replication and cytokinesis. However, the genetic bases and evolutionary processes underlying this 'molecular diversity' remain to be explained. Here, we review a tool to generate alternative mechanisms for conserved cellular functions and test hypotheses concerning the generation of molecular diversity -evolutionary repair experiments, in which laboratory microbial populations adapt in response to a genetic perturbation. We summarize the insights gained from evolutionary repair experiments, the spectrum and dynamics of compensatory mutations, and the alternative molecular mechanisms used to repair perturbed cellular functions. We relate these experiments to the modifications of conserved functions that have occurred outside the laboratory. We end by proposing strategies to improve evolutionary repair experiments as a tool to explore the molecular diversity of life.

Genome architecture shapes evolutionary adaptation to DNA replication stress

“…Our results therefore agree with previous reports observing declining adaptability across strains with different initial fitness but largely fail to observe diminishing return epistasis as a potential justification of this phenomenon. Our experiments and two previous evolutionary repair experiments (Hsieh et al, 2020;Laan et al, 2015) both show interactions that are approximately additive between different selected mutations. The reasons for this difference are currently unknown.…”

“…In natural populations, interference with DNA replication, through the fixation of deleterious mutations, perturbation by selfish genetic elements or toxins secreted by antagonistic organisms could generate similar evolutionary adaptation. The consequences of these evolutionary processes could rewire genome maintenance modules to alter cancer cells' physiology and generate molecular diversity in nature [105]. For these scenarios to be plausible, the evolutionary adaptation to DNA replication stress needs to happen over short timescales.…”

Genetic interaction network has a very limited impact on the evolutionary trajectories in continuous culture-grown populations of yeast

“…If a genetic interaction network is stable, it could be expected that the landscape resulting from that network has an impact on the trajectory of compensatory evolution in similar conditions and similar genetic backgrounds. The history of compensatory evolution studies is as old as microbial experimental evolution itself (for a review see [4]). Once a deleterious mutation is introduced in a given population, its negative effect on fitness can be alleviated through compensatory evolution.…”

“…Fig 4. Enriched GO terms in the biological process category among DEGs from evolved non-mutator (A) and mutator (B) strains…”

Evolutionary repair reveals an unexpected role of the tRNA modification m1G37 in aminoacylation

“…Evolutionary repair offers a methodology to address both of these hypotheses. In evolutionary repair experiments, a microbial strain is subjected to a genetic perturbation, usually gene deletion, and then propagated over hundreds to thousands of generations to allow the population to evolve in response to the perturbation (29). Next-generation sequencing (NGS) of population genomic DNA or whole-genome sequencing of isolated clones can be used to identify any adaptive mutations that alleviate the fitness defect caused by the original perturbation.…”