Mutation rate Evolution

Evolutionary dynamics in experimental mutator populations

Keywords: Adaptation - Evolutionary biology - Molecular Microbiology - Mutation Rates - Genomics Data

Figure: Fitness trajectory and mutation rate evolution in Ara-1

Mutation rate dynamics in a bacterial population reflect tension between adaptation and genetic load

We asked if and how mutation rates themselves evolve in the same long-term experimental evolution setting. According to theory, mutation rates should be minimized for well-adapted populations living in stable environments, whereas hypermutators may evolve if conditions change. However, the long-term fate of hypermutators is unknown. Using a phylogenomic approach, we found that an adapting Escherichia coli population that first evolved a mutT hypermutator phenotype relative to its ancestor was later invaded by two independent lineages with mutY mutations that reduced genome-wide mutation rates. Applying neutral theory to synonymous substitutions, we dated the emergence of these mutations and inferred that the mutT mutation increased the point-mutation rate by ∼150-fold, whereas the mutY mutations reduced the rate by ∼40–60%, with a corresponding decrease in the genetic load. Thus, the long-term fate of the hypermutators was governed by the selective advantage arising from a reduced mutation rate as the potential for further adaptation declined.
Figure: Microcolonies of REL606 (Ara-; red) and REL607 (Ara+;white) on tetrazolium agar

Mutation Rate Inferred From Synonymous Substitutions in a Long-Term Evolution Experiment With Escherichia coli

The quantification of spontaneous mutation rates is crucial for a mechanistic understanding of the evolutionary process. In bacteria, traditional estimates using experimental or comparative genetic methods are prone to statistical uncertainty and consequently estimates vary by over one order of magnitude. With the advent of next-generation sequencing, more accurate estimates are now possible. Initially, 19 Escherichia coli genomes were sequenced from a 40,000-generation evolution experiment and the point-mutation rate were directly inferred based on the accumulation of synonymous substitutions. The resulting estimate was 8.9 x 10-11 per base-pair per generation, and there was a significant bias toward increased AT-content (Wielgoss et al. 2011).