Review Article | Published:

Genome dynamics during experimental evolution

Nature Reviews Genetics volume 14, pages 827839 (2013) | Download Citation


Evolutionary changes in organismal traits may occur either gradually or suddenly. However, until recently, there has been little direct information about how phenotypic changes are related to the rate and the nature of the underlying genotypic changes. Technological advances that facilitate whole-genome and whole-population sequencing, coupled with experiments that 'watch' evolution in action, have brought new precision to and insights into studies of mutation rates and genome evolution. In this Review, we discuss the evolutionary forces and ecological processes that govern genome dynamics in various laboratory systems in the context of relevant population genetic theory, and we relate these findings to evolution in natural populations.

Key points

  • New DNA sequencing technologies are being used to characterize whole-genome and whole-population dynamics during experimental evolution studies at a new level of resolution. Population genetic theory, including differences between asexual and sexual modes of reproduction, is crucial to interpreting these data.

  • Spontaneous mutation rates that are caused by DNA replication and repair errors can be measured with great precision by sequencing mutation accumulation experiments, in which parallel lineages are propagated through population bottlenecks so that evolution is effectively random with respect to mutational effects on fitness.

  • By contrast, adaptive evolution experiments provide insights into both the genetic basis and dynamics of adaptation. Genomic analyses show that adaptation rarely occurs by periodic sweeps of single beneficial mutations through asexual populations. Rather, divergent paths that involve multiple mutations are often explored before any one evolved type can displace its competitors.

  • The long-term fates of mutations may depend not only on their immediate effects on competitive fitness but also on second-order selection for evolvability. This process requires sufficient population sizes and genetic diversity so that multi-step mutational pathways are explored, and it may be mediated either by mutation rates or by epistasis.

  • Co-evolutionary interactions can promote genetic diversity in populations and accelerate the rate of genomic evolution. Complex ecological interactions, such as cross-feeding, often evolve even in simple environments.

  • New combinations of alleles derived from standing genetic diversity rather than de novo mutations can drive genetic dynamics during adaptation in sexually reproducing populations.

  • Laboratory evolution experiments provide a framework for interpreting genome dynamics observed during the evolution of both microbial pathogens and cancers in human disease.

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The authors thank the reviewers for their suggestions. They acknowledge support from the US National Institutes of Health (R00-GM087550 to J.E.B.), the US National Science Foundation (NSF; DEB-1019989 to R.E.L.) and the BEACON Center for the Study of Evolution in Action (NSF Cooperative Agreement DBI-0939454 to J.E.B. and R.E.L.).

Author information


  1. Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, The University of Texas, Austin, Texas 78712, USA.

    • Jeffrey E. Barrick
  2. BEACON Center for the Study of Evolution in Action, Michigan State University, East Lansing, Michigan 48824, USA.

    • Jeffrey E. Barrick
    •  & Richard E. Lenski
  3. Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, USA.

    • Richard E. Lenski


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Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Jeffrey E. Barrick or Richard E. Lenski.


Mutation accumulation

A type of evolution experiment in which populations are deliberately forced through a bottleneck of one or a few breeding individuals, which allows non-lethal mutations to accumulate with little or no filtering by natural selection.

Population bottlenecks

Reductions in population size that typically also reduce genetic diversity. Bottlenecks can be deliberately imposed, such as in a mutation accumulation experiment. Cryptic bottlenecks also arise as a consequence of selective sweeps, especially in asexual populations, that drive out competing lineages and thus reduce genetic diversity.

Mutation rate

The rate at which new genetic mutations spontaneously occur during the replication and transmission of genetic information from parent to offspring.

Substitution rate

The rate at which new mutations accumulate in an evolving lineage over time, which typically depends on both the mutation rate and the effects of natural selection.

Biological fitness

A quantitative measure of the contribution of a specific organism or genotype to future generations owing to differential survival, reproduction or both, that is associated with its phenotype; fitness is often expressed relative to other organisms or genotypes.

Diminishing-returns epistasis

Interactions among mutations such that the combined effect of the mutations on fitness or on some other trait is less than that expected from their individual contributions.

All-or-none epistasis

Interactions among mutations such that an entire set of mutations is required to confer a fitness advantage or a new trait; no subset that lacks one of these mutations has the advantage or an intermediate form of the relevant trait.

Adaptive evolution

Evolution under conditions in which surviving organisms accumulate genetic changes that lead to a fitness advantage over their progenitors.

Fitness landscape

The visualization of the genotype-to-fitness mapping for an organism in which the height of a position on the map represents the fitness of that genotype and the location is a reduced-dimensional projection of possible genotypes. An evolutionary trajectory of genetic changes can be visualized as a 'walk' and adaptation as a 'climb' in the fitness landscape.

Selective sweep

The increase in the frequency of an advantageous allele in a population as it displaces ancestral and competitor alleles.

Genetic fixation

The point at which an allele has completely displaced ancestral and competitor alleles; that is, the allele is present in every surviving individual in the population.

Periodic selection

The phenomenon whereby successive beneficial mutations completely sweep through an evolving population. Other mutations that are linked, but are not beneficial, can hitchhike with the beneficial driver mutation.

Clonal interference

Competition between lineages that have different beneficial mutations in asexual populations, which slows the rate at which any particular allele fixes in the population relative to a freely recombining population.

Long-term evolution experiment

(LTEE). An experiment with Escherichia coli that has surpassed 25 years and 55,000 generations in duration.

Genetic background

The genotype of an organism; that is, its complete genome sequence or the alleles that distinguish it from other organisms.

Strength of selection

The benefit of accessible beneficial mutations relative to current mean population fitness. Under strong selection, sweeps of new genotypes generally occur more rapidly, and less diversity builds up in a population.

Genetic load

The indirect fitness cost to an organism caused by producing offspring with mutations that either reduce their fitness or are lethal.

Genetic architecture

The properties of an organism, including its metabolic, regulatory and developmental pathways, that determine how new mutations affect phenotypes and fitness.

Isogenic construct

An organism, produced in the laboratory using various genetic tools, that has defined genetic differences from a reference organism. It is used to study the effects on fitness and on other phenotypic traits of single mutations or combinations of mutations.

Niche construction

The production of a new resource or other ecological opportunity that is caused by the actions or evolution of organisms.

Metagenomic sequencing

The sequencing of DNA fragments that are randomly derived from a population containing a mixture of many genotypes.

Negative frequency dependence

An allele (or a trait) that undergoes a decline in fitness as it becomes more common in a population. If the allele confers an advantage when it is rare but is disadvantageous when it is common, then a genetic polymorphism is stably maintained.

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