Organisms inhabiting different environments are often locally adapted, and yet despite a considerable body of theory, the genetic basis of local adaptation is poorly understood. Unanswered questions include the number and effect sizes of adaptive loci, whether locally favored loci reduce fitness elsewhere (i.e., fitness tradeoffs), and whether a lack of genetic variation limits adaptation. To address these questions, we mapped quantitative trait loci (QTL) for total fitness in 398 recombinant inbred lines derived from a cross between locally adapted populations of the highly selfing plant Arabidopsis thaliana from Sweden and Italy and grown for 3 consecutive years at the parental sites (>40,000 plants monitored). We show that local adaptation is controlled by relatively few genomic regions of small to modest effect. A third of the 15 fitness QTL we detected showed evidence of tradeoffs, which contrasts with the minimal evidence for fitness tradeoffs found in previous studies. This difference may reflect the power of our multiyear study to distinguish conditionally neutral QTL from those that reflect fitness tradeoffs. In Sweden, but not in Italy, the local genotype underlying fitness QTL was often maladaptive, suggesting that adaptation there is constrained by a lack of adaptive genetic variation, attributable perhaps to genetic bottlenecks during postglacial colonization of Scandinavia or to recent changes in selection regime caused by climate change. Our results suggest that adaptation to markedly different environments can be achieved through changes in relatively few genomic regions, that fitness tradeoffs are common, and that lack of genetic variation can limit adaptation.O rganisms inhabiting different environments are often locally adapted, as demonstrated by experiments showing that local populations grown in their native sites outperform other populations (1-3). Despite a large body of theory, the genetic basis of local adaptation is poorly understood. Key unanswered questions include the number and effect sizes of adaptive loci, whether locally favored loci reduce fitness elsewhere (i.e., fitness tradeoffs), and whether the adaptive potential of populations is limited by insufficient genetic variation (4-11). The Fisherian view that adaptation is a function of many genes of small effect (12) has been challenged on theoretical grounds (4, 6), and recent empirical work indicates that genes with both large and small phenotypic effects contribute to differentiation in putatively adaptive traits (e.g., refs. 8 and 13). However, there are few direct estimates of the number of loci underlying fitness variation in native environments (14).Because natural environments are variable in both time and space, temporally replicated experiments are particularly important for distinguishing whether adaptive alleles are conditionally neutral [i.e., favored locally but neutral elsewhere (7, 15)] or are favored in one environment but disfavored in the other, reflecting an adaptive tradeoff (2, 7, 16). Evidence for conditi...

olyploidy or whole-genome duplication provides genomic opportunities for evolutionary innovations in many animal groups and all flowering plants 1-5 , including most important crops such as wheat, cotton and canola or oilseed rape 6-8. The common occurrence of polyploidy may suggest its advantage and potential for selection and adaptation 2,3,9 , through rapid genetic and genomic changes as observed in newly formed Brassica napus 10 , Tragopogon miscellus 11 and polyploid wheat 12 , and/or largely epigenetic modifications as in Arabidopsis and cotton polyploids 5,13. Cotton is a powerful model for revealing genomic insights into polyploidy 3 , providing a phylogenetically defined framework of polyploidization (~1.5 million years ago (Ma)) 14 , followed by natural diversification and crop domestication 15. The evolutionary history of the polyploid cotton clade is longer than that of some other allopolyploids, such as hexaploid wheat (~8,000 years) 12 , tetraploid canola (~7,500 years) 16 and tetraploid Tragopogon (~150 years) 11. Polyploidization between an A-genome African species (Gossypium arboreum (Ga)-like) and a D-genome American species (G. raimondii (Gr)-like) in the New World created a new allotetraploid or amphidiploid (AD-genome) cotton clade (Fig. 1a) 14 , which has diversified into five polyploid lineages, G. hirsutum (Gh) (AD) 1 , G. barbadense (Gb) (AD) 2 , G. tomentosum (Gt) (AD) 3 , G. mustelinum (Gm) (AD) 4 and G. darwinii (Gd) (AD) 5. G. ekmanianum and G. stephensii are recently characterized and closely related to Gh 17. Gh and Gb were separately domesticated from perennial shrubs to become annualized Upland and Pima cottons 15. To date, global cotton production provides income for ~100 million families across ~150 countries, with an annual economic impact of ~US$500 billion worldwide 6. However, cotton supply is reduced due to aridification, climate change and pest emergence. Future improvements in cotton and sustainability will involve use of the genomic resources and gene-editing tools becoming available in many crops 9,18,19. Cotton genomes have been sequenced for the D-genome (Gr) 20 and A-genome (Ga) 21 diploids and two cultivated tetraploids 22-26. These analyses have shown structural, genetic and gene expression variation related to fiber traits and stress responses in cultivated

Environmental stress is a major driver of ecological community dynamics and agricultural productivity. This is especially true for soil water availability, because drought is the greatest abiotic inhibitor of worldwide crop yields. Here, we test the genetic basis of drought responses in the genetic model for C4 perennial grasses, Panicum hallii, through population genomics, field-scale gene-expression (eQTL) analysis, and comparison of two complete genomes. While gene expression networks are dominated by local cis-regulatory elements, we observe three genomic hotspots of unlinked trans-regulatory loci. These regulatory hubs are four times more drought responsive than the genome-wide average. Additionally, cis- and trans-regulatory networks are more likely to have opposing effects than expected under neutral evolution, supporting a strong influence of compensatory evolution and stabilizing selection. These results implicate trans-regulatory evolution as a driver of drought responses and demonstrate the potential for crop improvement in drought-prone regions through modification of gene regulatory networks.

An evolutionary response to selection requires genetic variation; however, even if it exists, then the genetic details of the variation can constrain adaptation. In the simplest case, unlinked loci and uncorrelated phenotypes respond directly to multivariate selection and permit unrestricted paths to adaptive peaks. By contrast, ‘antagonistic’ pleiotropic loci may constrain adaptation by affecting variation of many traits and limiting the direction of trait correlations to vectors that are not favoured by selection. However, certain pleiotropic configurations may improve the conditions for adaptive evolution. Here, we present evidence that the Arabidopsis thaliana gene FRI (FRIGIDA) exhibits ‘adaptive’ pleiotropy, producing trait correlations along an axis that results in two adaptive strategies. Derived, low expression FRI alleles confer a ‘drought escape’ strategy owing to fast growth, low water use efficiency and early flowering. By contrast, a dehydration avoidance strategy is conferred by the ancestral phenotype of late flowering, slow growth and efficient water use during photosynthesis. The dehydration avoidant phenotype was recovered when genotypes with null FRI alleles were transformed with functional alleles. Our findings indicate that the well-documented effects of FRI on phenology result from differences in physiology, not only a simple developmental switch.