Whole genome duplication (WGD, polyploidization) is arguably the most massive genome-wide mutation whose ubiquity across eukaryotes suggests an adaptive benefit, though no mechanism has been identified. Consequently, a large controversy dominates the field whether WGD represents net benefit or detriment to evolutionary success. I will test if WGD promotes adaptation in natural populations and address the underlying mechanism by estimating net fitness benefit of WGD vs. the role of post-WGD accumulation of adaptive variation. This question has not been satisfactorily addressed before because experimental studies of WGD were disconnected from field surveys and population genomics avoided complex polyploid genomes. Only recently, we have shown a proof-of-concept that WGD can increase the capacity of populations to accumulate adaptive variation in wild Arabidopsis. Yet the underlying mechanism still remains unknown. I will address the adaptive consequences of WGD over a hierarchy of levels: genome, phenotype, population and species. In six naturally ploidy-variable plant species I plan to test if (i) natural polyploid populations accumulate larger adaptive variation than diploids (ii) WGD per se or post-WGD evolution brings important adaptive novelties (iii) rates of positive selection increase after WGD To achieve these goals, I will combine ecological genomics of natural populations with evolve-and-resequence experiments. To move beyond single-species correlative studies, I will manipulate the mutation itself via synthesis of neo-polyploid individuals and populations in six species. Then I will compare adaptation signals in genomes and phenotypes of synthetic polyploids and their natural diploid and tetraploid relatives. This project will determine the adaptive value of WGD, an important force in evolution and crop domestication, with the ambition to improve our understanding of the role of large genomic mutations in natural selection and adaptation.