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Long‐term genetic studies of wild populations are very scarce, but are essential for connecting ecological and population genetics models, and for understanding the dynamics of biodiversity. We present a study of a wild wheat population sampled over a 36‐year period at high spatial resolution. We genotyped 832 individuals from regular sampling along transects during the course of the experiment. Genotypes were clustered into ecological microhabitats over scales of tens of metres, and this clustering was remarkably stable over the 36 generations of the study. Simulations show that it is difficult to determine whether this spatial and temporal stability reflects extremely limited dispersal or fine‐scale local adaptation to ecological parameters. Using a common‐garden experiment, we showed that the genotypes found in distinct microhabitats differ phenotypically. Our results provide a rare insight into the population genetics of a natural population over a long monitoring period. [ABSTRACT FROM AUTHOR]

Centromeres are critical for cell division, loading CENH3 or CENPA histone variant nucleosomes, directing kinetochore formation and allowing chromosome segregation1,2. Despite their conserved function, centromere size and structure are diverse across species. To understand this centromere paradox3,4, it is necessary to know how centromeric diversity is generated and whether it reflects ancient trans-species variation or, instead, rapid post-speciation divergence. To address these questions, we assembled 346 centromeres from 66 Arabidopsis thaliana and 2 Arabidopsis lyrata accessions, which exhibited a remarkable degree of intra- and inter-species diversity. A. thaliana centromere repeat arrays are embedded in linkage blocks, despite ongoing internal satellite turnover, consistent with roles for unidirectional gene conversion or unequal crossover between sister chromatids in sequence diversification. Additionally, centrophilic ATHILA transposons have recently invaded the satellite arrays. To counter ATHILA invasion, chromosome-specific bursts of satellite homogenization generate higher-order repeats and purge transposons, in line with cycles of repeat evolution. Centromeric sequence changes are even more extreme in comparison between A. thaliana and A. lyrata. Together, our findings identify rapid cycles of transposon invasion and purging through satellite homogenization, which drive centromere evolution and ultimately contribute to speciation.Inter- and intra-species comparison of Arabidopsis centromere variation identifies rapid cycles of transposon invasion and purging through satellite homogenization that drive centromere evolution. [ABSTRACT FROM AUTHOR]

Gene-body methylation (gbM) refers to sparse CG methylation of coding regions, which is especially prominent in evolutionarily conserved house-keeping genes. It is found in both plants and animals, but is directly and stably (epigenetically) inherited over multiple generations in the former. Studies in Arabidopsis thaliana have demonstrated that plants originating from different parts of the world exhibit genome-wide differences in gbM, which could reflect direct selection on gbM, but which could also reflect an epigenetic memory of ancestral genetic and/or environmental factors. Here we look for evidence of such factors in F2 plants resulting from a cross between a southern Swedish line with low gbM and a northern Swedish line with high gbM, grown at two different temperatures. Using bisulfite-sequencing data with nucleotide-level resolution on hundreds of individuals, we confirm that CG sites are either methylated (nearly 100% methylation across sampled cells) or unmethylated (approximately 0% methylation across sampled cells), and show that the higher level of gbM in the northern line is due to more sites being methylated. Furthermore, methylation variants almost always show Mendelian segregation, consistent with their being directly and stably inherited through meiosis. To explore how the differences between the parental lines could have arisen, we focused on somatic deviations from the inherited state, distinguishing between gains (relative to the inherited 0% methylation) and losses (relative to the inherited 100% methylation) at each site in the F2 generation. We demonstrate that deviations predominantly affect sites that differ between the parental lines, consistent with these sites being more mutable. Gains and losses behave very differently in terms of the genomic distribution, and are influenced by the local chromatin state. We find clear evidence for different trans-acting genetic polymorphism affecting gains and losses, with those affecting gains showing strong environmental interactions (G×E). Direct effects of the environment were minimal. In conclusion, we show that genetic and environmental factors can change gbM at a cellular level, and hypothesize that these factors can also lead to transgenerational differences between individuals via the inclusion of such changes in the zygote. If true, this could explain genographic pattern of gbM with selection, and would cast doubt on estimates of epimutation rates from inbred lines in constant environments. Author summary: Gene-body methylation, the sparse CG methylation that is associated with house-keeping genes, is found in both plants and animals, but can be directly inherited in the former. Recently, we discovered that Arabidopsis thaliana originating from different geographic regions exhibit different patterns of gbM, which could be due to direct selection on gbM, but could also reflect a transgenerational memory of genetic or environmental factors. Here we look for evidence of such factors using a genetic cross between two natural inbred lines: one with high, and one with low gbM. We confirm that methylation states are stably inherited, but also see large somatic deviations from the inherited state, in particular at sites that differ between the parental lines. We demonstrate that these deviations are affected by genetic variants in interaction with the environment, and hypothesize that geographic differences in gbM arise through the inclusion of such deviations in the zygote. [ABSTRACT FROM AUTHOR]

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 attack (1). 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 invasion (2-5). 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 environment (6-11). 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., A survey of A. thaliana accessions collected from the wild revealed extensive environment-dependent variation for leaf initiation rate (Supplementary Table 1). One of the strains, Est-1, which produced leaves more [...]

Although pioneered by human geneticists as a potential solution to the challenging problem of finding the genetic basis of common human diseases (1,2), 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 traits (3). 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., The genotyped sample (Supplementary Table 1) includes a core set of 95 lines (4) for which a wide variety of phenotypes were available, plus a second set of 96 lines [...]

Genome-wide association studies (GWAS) have revealed that the striking natural variation for DNA CHH-methylation (mCHH; H is A, T, or C) of transposons has oligogenic architecture involving major alleles at a handful of known methylation regulators. Here we use a conditional GWAS approach to show that CHG-methylation (mCHG) has a similar genetic architecture—once mCHH is statistically controlled for. We identify five key trans-regulators that appear to modulate mCHG levels, and show that they interact with a previously identified modifier of mCHH in regulating natural transposon mobilization. Author summary: DNA methylation is an epigenetic mark common across eukaryotes. It is associated with transcriptional silencing, in particular of transposable elements. Multiple elements, including epigenetic inheritance, shape DNA methylation patterns, and the complexity makes it challenging to dissect the regulation. Our work on the 1001 Arabidopsis Epigenomes project led to the unexpected discovery that much of the natural variation for CHH methylation (mCHH; H is A, T, or C) on transposable elements could be attributed to allelic variation in three genes known to be involved in epigenetic regulation. However, our analysis of methylation in other sequence contexts (mCHG and mCG) revealed no genetic regulator. Here we show that if mCHG variation is analyzed while taking mCHH into account, mCHG is also strongly influenced by allelic variation in a small number of genes with known or highly plausible direct roles in epigenetic regulation. The presence of common allelic variation of large effect is suggestive of some form of local adaptation. The nature of this adaptation remains obscure, but we present further evidence that allelic variation regulating DNA methylation influences transposon mobilization. [ABSTRACT FROM AUTHOR]

Natural variation presents one of the fundamental challenges of modern biology. Soon, the genome sequences of thousands of individuals will be known for each of several species. But how does the genotypic variation that will be observed among these individuals translate into phenotypic variation? Plants are in many ways ideal for addressing this question, and resources that are unmatched, except in humans, have now been developed., When it comes to dissecting complex traits, genetic studies of plants have always been at the forefront. Work with cereals provided the first demonstrations that segregation at multiple loci could [...]

We present an exact forward-in-time algorithm that can efficiently simulate the evolution of a finite population under the Wright-Fisher model. We used simulations based on this algorithm to verify the accuracy of the ancestral recombination graph approximation by comparing it to the exact Wright-Fisher scenario. We find that the recombination graph is generally a very good approximation for models with complete outcrossing, whereas, for models with self-fertilization, the approximation becomes slightly inexact for some combinations of selfing and recombination parameters.

The molecular basis for variation in vernalization in Arabidopsis natural accessions adapted to different climates is investigated. The results have shown that the variation in epigenetic silencing of the floral repressor gene FLOWERING LOCUS C (FLC) have contributed to Arabidopsis adaptation.

We describe a novel method for jointly estimating crossing-over and gene-conversion rates from population genetic data using summary statistics. The performance of our method was tested on simulated data sets and compared with the composite-likelihood method of R. R. Hudson. For several realistic parameter values, the new method performed similarly to the composite-likelihood approach for estimating crossing-over rates and better when estimating gene-conversion rates. We used our method to analyze a human data set recently genotyped by Perlegen Sciences.

In linkage disequilibrium mapping of genetic variants causally associated with phenotypes, spurious associations can potentially be generated by any of a variety of types of population structure. However, mathematical theory of the production of spurious associations has largely been restricted to population structure models that involve the sampling of individuals from a collection of discrete subpopulations. Here, we introduce a general model of spurious association in structured populations, appropriate whether the population structure involves discrete groups, admixture among such groups, or continuous variation across space. Under the assumptions of the model, we find that a single common principle-applicable to both the discrete and admixed settings as well as to spatial populations--gives a necessary and sufficient condition for the occurrence of spurious associations. Using a mathematical connection between the discrete and admixed cases, we show that in admixed populations, spurious associations are less severe than in corresponding mixtures of discrete subpopulations, especially when the variance of admixture across individuals is small. This observation, together with the results of simulations that examine the relative influences of various model parameters, has important implications for the design and analysis of genetic association studies in structured populations.

We develop methods for exploiting 'single-feature polymorphism' data, generated by hybridizing genomic DNA to oligonucleotide expression arrays. Our methods enable the use of such data, which can be regarded as very high density, but imperfect, polymorphism data, for genomewide association or linkage disequilibrium mapping. We use a simulation-based power study to conclude that our methods should have good power for organisms like Arabidopsis thaliana, in which linkage disequilibrium is extensive, the reason being that the noisiness of single-feature polymorphism data is more than compensated for by their great number. Finally, we show how power depends on the accuracy with which single-feature polymorphisms are called.