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? Combining experimental evolution with next-generation sequencing, the evolve and resequence (E&R) approach is a powerful method for dissecting the genomic changes underlying the adaptation of populations of laboratory organisms or molecules. This Review describes the E&R results from diverse systems and discusses the extent to which various features, including population genetics, experimental setups and reproduction modes, account for the distinct observed outcomes. 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