Large-scale genome-wide association (GWA) studies have become an important tool in human genomics, mostly focused on disease but also on adaptive variations such as skin colour. The technique is now shown to be similarly useful in plants. Atwell et al. report a GWA study of over a hundred phenotypes in naturally occurring inbred lines of Arabidopsis thaliana. The results range from significant associations, usually for single genes, to more difficult-to-interpret findings that indicate confounding by complex genetics and population structure. The accompanying paper by Todesco et al. demonstrates the ability of this technique to detect major-effect gene loci. Using forward genetics and GWA analyses, they show that variation at a single locus (ACD6) in Arabidopsis underlies phenotypic variation in vegetative growth as well as resistance to infection. The strong enhancement of resistance mediated by one of the alleles at this locus explains its persistence in natural populations throughout the world, despite it drastically reducing new leaf production. Here, large-scale genome-wide association studies were carried out with the naturally occurring inbred lines of Arabidopsis thaliana, which can be genotyped once and phenotyped repeatedly. The results range from significant associations, usually corresponding to single genes, to findings that are more difficult to interpret, because confounding by complex genetics and population structure makes it hard to distinguish true associations from false. Although pioneered by human geneticists as a potential solution to the challenging problem of finding the genetic basis of common human diseases1,2, genome-wide association (GWA) studies have, owing to advances in genotyping and sequencing technology, become an obvious general approach for studying the genetics of natural variation and traits of agricultural importance. They are particularly useful when inbred lines are available, because once these lines have been genotyped they can be phenotyped multiple times, making it possible (as well as extremely cost effective) to study many different traits in many different environments, while replicating the phenotypic measurements to reduce environmental noise. Here we demonstrate the power of this approach by carrying out a GWA study of 107 phenotypes in Arabidopsis thaliana, a widely distributed, predominantly self-fertilizing model plant known to harbour considerable genetic variation for many adaptively important traits3. Our results are dramatically different from those of human GWA studies, in that we identify many common alleles of major effect, but they are also, in many cases, harder to interpret because confounding by complex genetics and population structure make it difficult to distinguish true associations from false. However, a-priori candidates are significantly over-represented among these associations as well, making many of them excellent candidates for follow-up experiments. Our study demonstrates the feasibility of GWA studies in A. thaliana and suggests that the approach will be appropriate for many other organisms.

Hybridization may drive rare taxa to extinction through genetic swamping, where the rare form is replaced by hybrids, or by demographic swamping, where population growth rates are reduced due to the wasteful production of maladaptive hybrids. Conversely, hybridization may rescue the viability of small, inbred populations. Understanding the factors that contribute to destructive versus constructive outcomes of hybridization is key to managing conservation concerns. Here, we survey the literature for studies of hybridization and extinction to identify the ecological, evolutionary, and genetic factors that critically affect extinction risk through hybridization. We find that while extinction risk is highly situation dependent, genetic swamping is much more frequent than demographic swamping. In addition, human involvement is associated with increased risk and high reproductive isolation with reduced risk. Although climate change is predicted to increase the risk of hybridization‐induced extinction, we find little empirical support for this prediction. Similarly, theoretical and experimental studies imply that genetic rescue through hybridization may be equally or more probable than demographic swamping, but our literature survey failed to support this claim. We conclude that halting the introduction of hybridization‐prone exotics and restoring mature and diverse habitats that are resistant to hybrid establishment should be management priorities.

Large-scale genome-wide association (GWA) studies have become an important tool in human genomics, mostly focused on disease but also on adaptive variations such as skin colour. The technique is now shown to be similarly useful in plants. Atwell et al. report a GWA study of over a hundred phenotypes in naturally occurring inbred lines of Arabidopsis thaliana. The results range from significant associations, usually for single genes, to more difficult-to-interpret findings that indicate confounding by complex genetics and population structure. The accompanying paper by Todesco et al. demonstrates the ability of this technique to detect major-effect gene loci. Using forward genetics and GWA analyses, they show that variation at a single locus (ACD6) in Arabidopsis underlies phenotypic variation in vegetative growth as well as resistance to infection. The strong enhancement of resistance mediated by one of the alleles at this locus explains its persistence in natural populations throughout the world, despite it drastically reducing new leaf production. Here, a combination of forward genetics and genome-wide association analyses has been used to show that variation at a single genetic locus in Arabidopsis thaliana underlies phenotypic variation in vegetative growth as well as resistance to infection. The strong enhancement of resistance mediated by one of the alleles at this locus explains the allele's persistence in natural populations throughout the world, even though it drastically reduces the production of new leaves. Plants can defend themselves against a wide array of enemies, from microbes to large animals, yet there is great variability in the effectiveness of such defences, both within and between species. Some of this variation can be explained by conflicting pressures from pathogens with different modes of attack1. A second explanation comes from an evolutionary ‘tug of war’, in which pathogens adapt to evade detection, until the plant has evolved new recognition capabilities for pathogen invasion2,3,4,5. If selection is, however, sufficiently strong, susceptible hosts should remain rare. That this is not the case is best explained by costs incurred from constitutive defences in a pest-free environment6,7,8,9,10,11. Using a combination of forward genetics and genome-wide association analyses, we demonstrate that allelic diversity at a single locus, ACCELERATED CELL DEATH 6 (ACD6)12,13, underpins marked pleiotropic differences in both vegetative growth and resistance to microbial infection and herbivory among natural Arabidopsis thaliana strains. A hyperactive ACD6 allele, compared to the reference allele, strongly enhances resistance to a broad range of pathogens from different phyla, but at the same time slows the production of new leaves and greatly reduces the biomass of mature leaves. This allele segregates at intermediate frequency both throughout the worldwide range of A. thaliana and within local populations, consistent with this allele providing substantial fitness benefits despite its marked impact on growth.

Many targets of plant microRNAs (miRNAs) are thought to play important roles in plant physiology and development. However, because plant miRNAs are typically encoded by medium-size gene families, it has often been difficult to assess their precise function. We report the generation of a large-scale collection of knockdowns for Arabidopsis thaliana miRNA families; this has been achieved using artificial miRNA target mimics, a recently developed technique fashioned on an endogenous mechanism of miRNA regulation. Morphological defects in the aerial part were observed for ∼20% of analyzed families, all of which are deeply conserved in land plants. In addition, we find that non-cleavable mimic sites can confer translational regulation in cis. Phenotypes of plants expressing target mimics directed against miRNAs involved in development were in several cases consistent with previous reports on plants expressing miRNA–resistant forms of individual target genes, indicating that a limited number of targets mediates most effects of these miRNAs. That less conserved miRNAs rarely had obvious effects on plant morphology suggests that most of them do not affect fundamental aspects of development. In addition to insight into modes of miRNA action, this study provides an important resource for the study of miRNA function in plants. MiRNAs are small RNA molecules that play an important role in regulating gene function, both in animals and in plants. In plants, miRNA target mimicry is an endogenous mechanism used to negatively regulate the activity of a specific miRNA family, through the production of a false target transcript that cannot be cleaved. This mechanism can be engineered to target different miRNA families. Using this technique, we have generated artificial target mimics predicted to reduce the activity of most of the miRNA families in Arabidopsis thaliana and have observed their effects on plant development. We found that deeply conserved miRNAs tend to have a strong impact on plant growth, while more recently evolved ones had generally less obvious effects, suggesting either that they primarily affect processes other than development, or else that they have more subtle or conditional functions or are even dispensable. In several cases, the effects on plant development that we observed closely resembled those seen in plants expressing miRNA–resistant versions of the major predicted targets, indicating that a limited number of targets mediates most effects of these miRNAs. Analyses of mimic expressing plants also support that plant miRNAs affect both transcript stability and protein accumulation. The artificial target mimic collection will be a useful resource to further investigate the function of individual miRNA families.