Modelling the genetic architecture of flowering time control in barley through nested association mapping

Background

Barley, globally the fourth most important cereal, provides food and beverages for humans and feed for animal husbandry. Maximizing grain yield under varying climate conditions largely depends on the optimal timing of flowering. Therefore, regulation of flowering time is of extraordinary importance to meet future food and feed demands. We developed the first barley nested association mapping (NAM) population, HEB-25, by crossing 25 wild barleys with one elite barley cultivar, and used it to dissect the genetic architecture of flowering time.

Results

Upon cultivation of 1,420 lines in multi-field trials and applying a genome-wide association study, eight major quantitative trait loci (QTL) were identified as main determinants to control flowering time in barley. These QTL accounted for 64% of the cross-validated proportion of explained genotypic variance (p_G). The strongest single QTL effect corresponded to the known photoperiod response gene Ppd-H1. After sequencing the causative part of Ppd-H1, we differentiated twelve haplotypes in HEB-25, whereof the strongest exotic haplotype accelerated flowering time by 11 days compared to the elite barley haplotype. Applying a whole genome prediction model including main effects and epistatic interactions allowed predicting flowering time with an unmatched accuracy of 77% of cross-validated p_G.

Conclusions

The elaborated causal models represent a fundamental step to explain flowering time in barley. In addition, our study confirms that the exotic biodiversity present in HEB-25 is a valuable toolbox to dissect the genetic architecture of important agronomic traits and to replenish the elite barley breeding pool with favorable, trait-improving exotic alleles.

     

When sinks become sources: Adaptive colonization in asexuals*

The establishment of a population into a new empty habitat outside of its initial niche is a phenomenon akin to evolutionary rescue in the presence of immigration. It underlies a wide range of processes, such as biological invasions by alien organisms, host shifts in pathogens, or the emergence of resistance to pesticides or antibiotics from untreated areas. We derive an analytically tractable framework to describe the evolutionary and demographic dynamics of asexual populations in a source-sink system. We analyze the influence of several factors on the establishment success in the sink, and on the time until establishment. To this aim, we use a classic phenotype-fitness landscape (Fisher's geometrical model in n dimensions) where the source and sink habitats have different phenotypic optima. In case of successful establishment, the mean fitness in the sink follows a typical four-phases trajectory. The waiting time to establishment is independent of the immigration rate and has a “U-shaped” dependence on the mutation rate, until some threshold where lethal mutagenesis impedes establishment and the sink population remains so. We use these results to get some insight into possible effects of several management strategies.     

RATES OF FITNESS DECLINE AND REBOUND SUGGEST PERVASIVE EPISTASIS

Unraveling the factors that determine the rate of adaptation is a major question in evolutionary biology. One key parameter is the effect of a new mutation on fitness, which invariably depends on the environment and genetic background. The fate of a mutation also depends on population size, which determines the amount of drift it will experience. Here, we manipulate both population size and genotype composition and follow adaptation of 23 distinct Escherichia coli genotypes. These have previously accumulated mutations under intense genetic drift and encompass a substantial fitness variation. A simple rule is uncovered: the net fitness change is negatively correlated with the fitness of the genotype in which new mutations appear—a signature of epistasis. We find that Fisher's geometrical model can account for the observed patterns of fitness change and infer the parameters of this model that best fit the data, using Approximate Bayesian Computation. We estimate a genomic mutation rate of 0.01 per generation for fitness altering mutations, albeit with a large confidence interval, a mean fitness effect of mutations of ?0.01, and an effective number of traits nine in mutS^? E. coli. This framework can be extended to confront a broader range of models with data and test different classes of fitness landscape models.     

THE ACTION OF STABILIZING SELECTION,MUTATION, AND DRIFT ON EPISTATIC QUANTITATIVE TRAITS

For a quantitative trait under stabilizing selection, the effect of epistasis on its genetic architecture and on the changes of genetic variance caused by bottlenecking were investigated using theory and simulation. Assuming empirical estimates of the rate and effects of mutations and the intensity of selection, we assessed the impact of two‐locus epistasis (synergistic/antagonistic) among linked or unlinked loci on the distribution of effects and frequencies of segregating loci in populations at the mutation‐selection‐drift balance. Strong pervasive epistasis did not modify substantially the genetic properties of the trait and, therefore, the most likely explanation for the low amount of variation usually accounted by the loci detected in genome‐wide association analyses is that many causal loci will pass undetected. We investigated the impact of epistasis on the changes in genetic variance components when large populations were subjected to successive bottlenecks of different sizes, considering the action of genetic drift, operating singly (D), or jointly with mutation (MD) and selection (MSD). An initial increase of the different components of the genetic variance, as well as a dramatic acceleration of the between‐line divergence, were always associated with synergistic epistasis but were strongly constrained by selection.     

Little Evidence for Synergism Among Deleterious Mutations in a Nonsegmented RNA Virus

Several models have been proposed to account for the segmentation of RNA viruses. One of the best known models suggests that segmentation, and mixing of segments during coinfections, is a way to eliminate deleterious mutations from the genome. However, for validity, this model requires that deleterious mutations interact in a synergistic way. That is, two mutations together should have a more deleterious effect than the result of adding their individual effects. Here I present evidence that deleterious mutations in foot-and-mouth disease virus produce a decline in fitness but that the relationship between the number of mutations fixed and the magnitude of fitness decline is compatible mainly with a nonsynergistic model. However, the statistical uncertainties associated with the data still give some room for the existence of very weak synergistic epistasis. Received: 2 November 1998 / Accepted: 19 April 1999     

The high level of wide-compatibility of variety ‘Dular’ has a complex genetic basis

Wide-compatibility varieties (WCVs) are a special class of rice germplasm that is able to produce fertile hybrids when crossed to both indica and japonica rice varieties. WCVs may differ greatly in their spectrum and level of compatibility. The objective of this study was to determine the genetic basis of wide-compatibility conferred by ‘Dular’, a landrace variety from India that has demonstrated a high level of wide-compatibility in previous studies with a broad range of indica and japonica varieties. A three-way cross (‘Balilla/Dular//Nanjing 11’) was made and the resulting F₁ population evaluated in the field for spikelet fertility. A total of 235 plants from this population was assayed individually for restriction fragment length polymorphisms (RFLPs) at 159 marker loci covering the entire rice genome at regular intervals. Quantitative trait locus (QTL) analysis identified 5 loci, located on chromosomes 1, 3, 5, 6 and 8, as having significant effects on hybrid fertility, which jointly explained 55.5% of the fertility variation in this population. The QTL on chromosome 5 ( f5) showed the largest effect on hybrid fertility, followed by those on chromosomes 6 ( f6), 3 ( f3) and 1 ( f1), with the one on chromosome 8 ( f8) having the smallest effect. Genotypes each composed of an allele from ‘Dular’ and an allele from ‘Nanjing 11’ at four ( f3, f5, f6 and f8) of the five QTLs contributed to the increase of fertility in the population. In contrast, the genotype composed of alleles from ‘Balilla’ and ‘Nanjing 11’ at the fifth locus ( f1) was in the direction of increasing fertility. Analysis of variance using marker genotypes at the five QTLs as the groups detected two interactions involving four of the five loci, a 2-locus interaction between f5 and f8 and a 3-locus interaction among f3, f5 and f6. The level of hybrid fertility is the result of complex interactions among these loci. The implication of the present findings in the utilization of the wide-compatibility of ‘Dular’ in rice breeding programs is also discussed. Received: 21 October 1997 / Accepted: 30 December 1997     

Genetic incompatibilities in killifish and the role of environment

Measuring reproductive isolation across multiple generations and environments is a key endeavor in speciation research because it indicates which isolating barriers currently prevent introgression and the extent to which they are intrinsic versus environmentally dependent. Here, I present data from several crosses (parental crosses, F1s, F2s, back-crosses) between two species of killifish (Lucania goodei and L. parva) that have diverged along a salinity gradient (L. goodei--freshwater, L. parva--euryhaline). Offspring were raised under high and low salinity to test for (1) extrinsic isolation, (2) intrinsic isolation manifested through genetic incompatibilities, and (3) environmentally dependent genetic incompatibilities. I found evidence for both intrinsic and extrinsic isolation, but no evidence for environmentally dependent genetic incompatibilities. The presence of extrinsic and intrinsic isolation varied among fitness measures, and all forms of reproductive isolation were asymmetric. Early egg survival was independent of salinity, but demonstrated pronounced intrinsic isolation. Both extrinsic and intrinsic isolation existed for egg hatching and survival of fry to the eating stage. Unfortunately, the order in which extrinsic and intrinsic isolation arose is unresolved. Understanding the extent to which adaptation to salinity creates multiple forms of reproductive isolation is critical for understanding diversification in many fish taxa.     

Mapping QTLs with digenic epistasis under multiple environments and predicting heterosis based on QTL effects

Mixed linear model approach was proposed for mapping QTLs with the digenic epistasis and QTL by environment (QE) interaction as well as additive and dominant effects. Monte Carlo simulations indicated that the proposed method could provide unbiased estimations for both positions and genetic main effects of QTLs, as well as unbiased predictions for QE interaction effects. A method was suggested for predicting heterosis based on individual QTL effects. The immortalized F₂ (IF₂) population constructed by random mating among RI or DH lines is appropriate for mapping QTLs with epistasis and their QE interaction. Based on the models and methodology proposed, we developed a QTL mapping software, QTLMapper 2.0 on the basis of QTLmapper 1.0, which is suitable for analyzing populations of DH, RIL, F₂ and IF₂. Data of thousand grain weight of IF₂ population with 240 lines derived from elite hybrid rice Shanyou 63 were analyzed as a worked example.     

Compensatory vs. pseudocompensatory evolution in molecular and developmental interactions

The evolution of molecules, developmental circuits, and new species are all characterized by the accumulation of incompatibilities between ancestors and descendants. When specific interactions between components are necessary at any of these levels, this requires compensatory coevolution. Theoretical treatments of compensatory evolution that only consider the endpoints predict that it should be rare because intermediate states are deleterious. However, empirical data suggest that compensatory evolution is common at all levels of molecular interaction. A general solution to this paradox is provided by plausible neutral or nearly neutral intermediates that possess informational redundancy. These intermediates provide an evolutionary path between coadapted allelic combinations. Although they allow incompatible end points to evolve, at no point was a deleterious mutation ever in need of compensation. As a result, what appears to be compensatory evolution may often actually be “pseudocompensatory.” Both theoretical and empirical studies indicate that pseudocompensation can speed the evolution of intergenic incompatibility, especially when driven by adaptation. However, under strong stabilizing selection the rate of pseudocompensatory evolution is still significant. Important examples of this process at work discussed here include the evolution of rRNA secondary structures, intra- and inter-protein interactions, and developmental genetic pathways. Future empirical work in this area should focus on comparing the details of intra- and intergenic interactions in closely related organisms.