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Elucidating the molecular architecture of adaptation via evolve and resequence experiments

Key Points

  • The evolve and resequence (E&R) approach is a powerful paradigm for understanding the molecular basis of adaptation.

  • Several E&R systems exist, ranging from in vitro RNA and DNA molecules to microorganisms evolving from an isogenic clone and sexual eukaryotes harbouring standing variation. E&R experiments are producing different results in the different systems. Can observed differences be reconciled with evolutionary theoretical models?

  • The systems differ in: population size, level of standing variation, initial variance in fitness and level of genetic exchange. We argue that when these differences between systems are taken into account many of the apparent differences can be explained.

  • Nevertheless, enigmas remain. Why do ploidy changes and/or large duplications and deletions seem to be more important in asexual microorganisms and sexual eukaryotes? At what point do sexually reproducing organisms need newly arising mutations? In sexually reproducing organisms, does allele frequency change often plateau before fixation? How much can macroscopic epistasis help us to understand evolution in microorganisms, and what is the role of epistasis in sexually reproducing organisms?

Abstract

Evolve and resequence (E&R) experiments use experimental evolution to adapt populations to a novel environment, then next-generation sequencing to analyse genetic changes. They enable molecular evolution to be monitored in real time on a genome-wide scale. Here, we review the field of E&R experiments across diverse systems, ranging from simple non-living RNA to bacteria, yeast and the complex multicellular organism Drosophila melanogaster. We explore how different evolutionary outcomes in these systems are largely consistent with common population genetics principles. Differences in outcomes across systems are largely explained by different starting population sizes, levels of pre-existing genetic variation, recombination rates and adaptive landscapes. We highlight emerging themes and inconsistencies that future experiments must address.

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Figure 1: A conceptual experimental evolution experiment.
Figure 2: E&R experiments reveal the dynamics of adaptation on a genome-wide scale.
Figure 3: E&R experiments in sexually reproducing species.
Figure 4: The molecular bases of adaptation.

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Acknowledgements

This work was supported by: the Borchard Scholar-in-Residence Program; ATIP-Avenir (Centre national de la recherche scientifique (CNRS/INSERM) and Institut National de la Santé et de la Recherche Médicale), FP7-PEOPLE-2012-CIG (322035), L'Agence nationale de la recherche (ANR-13-BSV6-0006-01 and ANR-11-LABX-0028-01), ARC (SFI20111203947) and La Ligue contre le cancer; US National Science Foundation Molecular and Cellular Biosciences (MCB1330606); and the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) European Research Council grant 310944.

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Supplementary information S1 (box)

Simulation parameters used to generate data in figures 2 and 3. (PDF 44 kb)

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Glossary

Standing genetic variation

Pre-existing genetic diversity in a population of interest.

Selection coefficients

Measurements of the proportional change in the fitness of a genotype owing to a mutation (represented by the variable s). The fitness of that genotype is calculated as 1 – s.

Fixation

When an allele of an initially polymorphic locus or haplotype reaches 100% relative frequency in the population.

Ribozymes

RNA molecules that are capable of catalysing chemical reactions. Natural ribozymes include ribosomal RNAs, spliceosomal RNAs, RNase P RNA, self-splicing introns and self-cleaving ribozymes.

Haplotype

The ordered collection of alleles along a single chromosome.

Mutation accumulation experiments

Experiments in which an initially isogenic strain is propagated for many generations with severe population-size bottlenecking (often to a single cell or individual) without voluntary selection. The mutations that distinguish the accumulation strain from its ancestor can be used to estimate mutation rates.

Clonal interference

A phenomenon observed in asexually evolving systems. Owing to a lack of recombination, clones harbouring different combinations of mutations compete against one another to reach fixation.

Pleiotropic

A genetic change affecting more than one phenotype.

Average fitness

The average fitness of a population is defined as the weighted sum of the fitness values associated with each genotype, where the weights are the frequencies of those genotypes. In an in vitro evolution experiment, there could initially be several million genotypes, with the vast majority having fitness values close to zero.

Selective sweeps

When selection drives a genetic polymorphism to fixation, closely linked regions of the genome will follow along to fixation with the adaptive allele. The size of the swept region depends on the starting allele frequency of the beneficial allele, the strength of selection and the local recombination rate.

Aneuploidy

Having an abnormal chromosome number owing to gain or loss of entire chromosomes.

Tertiary interactions

Molecular interactions stabilizing the overall (tertiary) structure of a functional RNA.

Linkage disequilibrium

The condition in which the frequency of a particular haplotype for two loci is significantly different from that expected if the loci were assorting independently.

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Long, A., Liti, G., Luptak, A. et al. Elucidating the molecular architecture of adaptation via evolve and resequence experiments. Nat Rev Genet 16, 567–582 (2015). https://doi.org/10.1038/nrg3937

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