Towards identifying genes underlying ecologically relevant traits in Arabidopsis thaliana

A major challenge in evolutionary biology and plant breeding is to identify the genetic basis of complex quantitative traits, including those that contribute to adaptive variation. Here we review the development of new methods and resources to fine-map intraspecific genetic variation that underlies natural phenotypic variation in plants. In particular, the analysis of 107 quantitative traits reported in the first genome-wide association mapping study in Arabidopsis thaliana sets the stage for an exciting time in our understanding of plant adaptation. We also argue for the need to place phenotype–genotype association studies in an ecological context if one is to predict the evolutionary trajectories of plant species.

[1]  Judy H. Cho,et al.  Finding the missing heritability of complex diseases , 2009, Nature.

[2]  J. Keurentjes,et al.  Development of a Near-Isogenic Line Population of Arabidopsis thaliana and Comparison of Mapping Power With a Recombinant Inbred Line Population , 2007, Genetics.

[3]  Detlef Weigel,et al.  Next-generation genetics in plants , 2008, Nature.

[4]  D. Matthies,et al.  The spatial scale of adaptive population differentiation in a wide-spread, well-dispersed plant species , 2008 .

[5]  Joseph R. Ecker,et al.  Moving forward in reverse: genetic technologies to enable genome-wide phenomic screens in Arabidopsis , 2006, Nature Reviews Genetics.

[6]  J. Dangl,et al.  Structure of the Arabidopsis RPM1 gene enabling dual specificity disease resistance , 1995, Science.

[7]  Leonid Kruglyak,et al.  Dissection of genetically complex traits with extremely large pools of yeast segregants , 2010, Nature.

[8]  Zachary A. Szpiech,et al.  Genome-wide association studies in diverse populations , 2010, Nature Reviews Genetics.

[9]  T. Petes,et al.  Analysis of the Proteins Involved in the in Vivo Repair of Base–Base Mismatches and Four-Base Loops Formed During Meiotic Recombination in the Yeast Saccharomyces cerevisiae , 2006, Genetics.

[10]  Zhiwu Zhang,et al.  Association Mapping: Critical Considerations Shift from Genotyping to Experimental Design , 2009, The Plant Cell Online.

[11]  J. Schmitt,et al.  Environmental Effects on the Expression of Quantitative Trait Loci and Implications for Phenotypic Evolution , 2004 .

[12]  J. Borevitz,et al.  Genetics of Local Adaptation in the Laboratory: Flowering Time Quantitative Trait Loci under Geographic and Seasonal Conditions in Arabidopsis , 2006, PloS one.

[13]  M. Lynch,et al.  Genetics and Analysis of Quantitative Traits , 1996 .

[14]  M. Pigliucci,et al.  Epigenetics for ecologists. , 2007, Ecology letters.

[15]  T. Mitchell-Olds.  Complex-trait analysis in plants , 2010, Genome Biology.

[16]  A. Brice,et al.  A QTL for flowering time in Arabidopsis reveals a novel allele of CRY2 , 2002, Nature Genetics.

[17]  R. O’Malley,et al.  ARABIDOPSIS : A RICH HARVEST 10 YEARS AFTER COMPLETION OF THE GENOME SEQUENCE Linking genotype to phenotype using the Arabidopsis unimutant collection , 2011 .

[18]  E. Buckler,et al.  Quantitative trait loci analysis of growth response to varying nitrogen sources in Arabidopsis thaliana , 2002, Theoretical and Applied Genetics.

[19]  X. Reboud,et al.  DNA polymorphism at the FRIGIDA gene in Arabidopsis thaliana: extensive nonsynonymous variation is consistent with local selection for flowering time. , 2002, Molecular biology and evolution.

[20]  M. Nordborg,et al.  Sequence variation and haplotype structure surrounding the flowering time locus FRI in Arabidopsis thaliana. , 2002, Genetics.

[21]  Jonathan D. G. Jones,et al.  Genome-wide survey of Arabidopsis natural variation in downy mildew resistance using combined association and linkage mapping , 2010, Proceedings of the National Academy of Sciences.

[22]  Russell L. Malmberg,et al.  Epistasis for Fitness-Related Quantitative Traits in Arabidopsis thaliana Grown in the Field and in the Greenhouse , 2005, Genetics.

[23]  N. Scarcelli,et al.  Pleiotropic effects of environment-specific adaptation in Arabidopsis thaliana. , 2009, The New phytologist.

[24]  M. Nordborg,et al.  A Coastal Cline in Sodium Accumulation in Arabidopsis thaliana Is Driven by Natural Variation of the Sodium Transporter AtHKT1;1 , 2010, PLoS genetics.

[25]  D. Weigel,et al.  Identification of a Spontaneous Frame Shift Mutation in a Nonreference Arabidopsis Accession Using Whole Genome Sequencing1 , 2010, Plant Physiology.

[26]  P. Laird.  Principles and challenges of genome-wide DNA methylation analysis , 2010, Nature Reviews Genetics.

[27]  M. Durand-Tardif,et al.  A Focus on Natural Variation for Abiotic Constraints Response in the Model Species Arabidopsis thaliana , 2009, International journal of molecular sciences.

[28]  R. A. Fisher,et al.  The Genetical Theory of Natural Selection , 1931 .

[29]  Joy Bergelson,et al.  Association mapping of local climate-sensitive quantitative trait loci in Arabidopsis thaliana , 2010, Proceedings of the National Academy of Sciences.

[30]  M. Nordborg,et al.  Variation in the epigenetic silencing of FLC contributes to natural variation in Arabidopsis vernalization response. , 2006, Genes & development.

[31]  B. Han,et al.  High throughput DNA sequencing: The new sequencing revolution. , 2010, Plant science : an international journal of experimental plant biology.

[32]  Brook T. Moyers,et al.  Effects of Genetic Perturbation on Seasonal Life History Plasticity , 2009, Science.

[33]  J. Bergelson.  The Effects of Genotype and the Environment on Costs of Resistance in Lettuce , 1994, The American Naturalist.

[34]  F. Wielgolaski,et al.  Phenological modifications in plants by various edaphic factors , 2001, International journal of biometeorology.

[35]  J. Bergelson,et al.  Fitness consequences of infection of Arabidopsis thaliana with its natural bacterial pathogen Pseudomonas viridiflava , 2007, Oecologia.

[36]  T. Mitchell-Olds,et al.  Genetic mechanisms and evolutionary significance of natural variation in Arabidopsis , 2006, Nature.

[37]  T. Tscharntke,et al.  Effects of below- and above-ground herbivores on plant growth, flower visitation and seed set , 2003, Oecologia.

[38]  W. Armbruster,et al.  Causes of covariation of phenotypic traits among populations , 1996 .

[39]  A Henk,et al.  A Mutation within the Leucine-Rich Repeat Domain of the Arabidopsis Disease Resistance Gene RPS5 Partially Suppresses Multiple Bacterial and Downy Mildew Resistance Genes , 1998, Plant Cell.

[40]  D. Thomas,et al.  Gene–environment-wide association studies: emerging approaches , 2010, Nature Reviews Genetics.

[41]  Joy Bergelson,et al.  Linkage and Association Mapping of Arabidopsis thaliana Flowering Time in Nature , 2010, PLoS genetics.

[42]  J. Suzuki,et al.  Latitudinal variation in plant size and relative growth rate in Arabidopsis thaliana , 1998, Oecologia.

[43]  R. Mott,et al.  The 1001 Genomes Project for Arabidopsis thaliana , 2009, Genome Biology.

[44]  M. Metzker.  Sequencing technologies — the next generation , 2010, Nature Reviews Genetics.

[45]  A. Price,et al.  Believe it or not, QTLs are accurate! , 2006, Trends in plant science.

[46]  E. Simms,et al.  Botanical Defenses. (Book Reviews: Plant Resistance to Herbivores and Pathogens. Ecology, Evolution, and Genetics.) , 1992 .

[47]  A. Paterson,et al.  QTL mapping of naturally-occurring variation in flowering time of Arabidopsis thaliana , 1994, Molecular and General Genetics MGG.

[48]  R. Kassen.  The experimental evolution of specialists, generalists, and the maintenance of diversity , 2002 .

[49]  J. Cheverud,et al.  Antagonistic pleiotropic effects reduce the potential adaptive value of the FRIGIDA locus , 2007, Proceedings of the National Academy of Sciences.

[50]  J. Borevitz,et al.  Genetic and epigenetic dissection of cis regulatory variation. , 2007, Current opinion in plant biology.

[51]  Edward S. Buckler,et al.  TASSEL: software for association mapping of complex traits in diverse samples , 2007, Bioinform..

[52]  H. Piepho,et al.  Analysis of a Triple Testcross Design With Recombinant Inbred Lines Reveals a Significant Role of Epistasis in Heterosis for Biomass-Related Traits in Arabidopsis , 2007, Genetics.

[53]  H. A. Orr,et al.  The genetic theory of adaptation: a brief history , 2005, Nature Reviews Genetics.

[54]  J. Hermisson,et al.  The Genetic Basis of Phenotypic Adaptation I: Fixation of Beneficial Mutations in the Moving Optimum Model , 2009, Genetics.

[55]  Eric P. Xing,et al.  Multi-population GWA mapping via multi-task regularized regression , 2010, Bioinform..

[56]  E. Stahl,et al.  Evolutionary Dynamics of Plant R-Genes , 2001, Science.

[57]  V. Le Corre.  Variation at two flowering time genes within and among populations of Arabidopsis thaliana: comparison with markers and traits. , 2005, Molecular ecology.

[58]  M. Kreitman,et al.  Fitness costs of R-gene-mediated resistance in Arabidopsis thaliana , 2003, Nature.

[59]  Derek A. Roff,et al.  Contributions of genomics to life-history theory , 2007, Nature Reviews Genetics.

[60]  D. Byers.  Evolution in heterogeneous environments and the potential of maintenance of genetic variation in traits of adaptive significance , 2005, Genetica.

[61]  Alain Charcosset,et al.  MetaQTL: a package of new computational methods for the meta-analysis of QTL mapping experiments , 2007, BMC Bioinformatics.

[62]  M. Kreitman,et al.  Low Levels of Polymorphism in Genes That Control the Activation of Defense Response in Arabidopsis thaliana , 2008, Genetics.

[63]  Zhiwu Zhang,et al.  Mixed linear model approach adapted for genome-wide association studies , 2010, Nature Genetics.

[64]  Keyan Zhao,et al.  An Arabidopsis Example of Association Mapping in Structured Samples , 2006, PLoS genetics.

[65]  B. Stich.  Comparison of Mating Designs for Establishing Nested Association Mapping Populations in Maize and Arabidopsis thaliana , 2009, Genetics.

[66]  Alkes L. Price,et al.  New approaches to population stratification in genome-wide association studies , 2010, Nature Reviews Genetics.

[67]  K. Gardner,et al.  Identifying loci under selection across contrasting environments in Avena barbata using quantitative trait locus mapping , 2006, Molecular ecology.

[68]  Jonathan Flint,et al.  Genetic architecture of quantitative traits in mice, flies, and humans. , 2009, Genome research.

[69]  Keyan Zhao,et al.  A Nonparametric Test Reveals Selection for Rapid Flowering in the Arabidopsis Genome , 2006, PLoS biology.

[70]  T. Mackay,et al.  Novel loci control variation in reproductive timing in Arabidopsis thaliana in natural environments. , 2002, Genetics.

[71]  A. Trubuil,et al.  Quantitative trait loci controlling root growth and architecture in Arabidopsis thaliana confirmed by heterogeneous inbred family , 2005, Theoretical and Applied Genetics.

[72]  J. Stinchcombe,et al.  QTL architecture of resistance and tolerance traits in Arabidopsis thaliana in natural environments , 2003, Molecular ecology.

[73]  M. Sillanpää,et al.  Overview of techniques to account for confounding due to population stratification and cryptic relatedness in genomic data association analyses , 2011, Heredity.

[74]  R. Doerge,et al.  Epigenetic Natural Variation in Arabidopsis thaliana , 2007, PLoS biology.

[75]  M. Soller,et al.  Advanced intercross lines, an experimental population for fine genetic mapping. , 1995, Genetics.

[76]  C. Dillmann,et al.  Comparison of RFLP and morphological distances between maize Zea mays L. inbred lines. Consequences for germplasm protection purposes , 1997, Theoretical and Applied Genetics.

[77]  H. Scharr,et al.  Simultaneous phenotyping of leaf growth and chlorophyll fluorescence via GROWSCREEN FLUORO allows detection of stress tolerance in Arabidopsis thaliana and other rosette plants. , 2009, Functional plant biology : FPB.

[78]  J. Cheverud.  Genetics and analysis of quantitative traits , 1999 .

[79]  Detlef Weigel,et al.  SHOREmap: simultaneous mapping and mutation identification by deep sequencing , 2009, Nature Methods.

[80]  J. Kingsolver,et al.  Migration, local adaptation and the evolution of plasticity , 2002 .

[81]  H. Piepho,et al.  Heterosis for Biomass-Related Traits in Arabidopsis Investigated by Quantitative Trait Loci Analysis of the Triple Testcross Design With Recombinant Inbred Lines , 2007, Genetics.

[82]  C. Carlson,et al.  Mapping complex disease loci in whole-genome association studies , 2004, Nature.

[83]  Justin O. Borevitz,et al.  Global Analysis of Genetic, Epigenetic and Transcriptional Polymorphisms in Arabidopsis thaliana Using Whole Genome Tiling Arrays , 2008, PLoS genetics.

[84]  E. Stone,et al.  The genetics of quantitative traits: challenges and prospects , 2009, Nature Reviews Genetics.

[85]  M. McMullen,et al.  Genetic Design and Statistical Power of Nested Association Mapping in Maize , 2008, Genetics.

[86]  R. Amasino,et al.  Molecular analysis of FRIGIDA, a major determinant of natural variation in Arabidopsis flowering time. , 2000, Science.

[87]  D. Heckerman,et al.  Efficient Control of Population Structure in Model Organism Association Mapping , 2008, Genetics.

[88]  J. Bergelson,et al.  Quantitative fitness effects of infection in a gene-for-gene system. , 2009, The New phytologist.

[89]  J. Moen,et al.  An illustrated gardener's guide to transgenic Arabidopsis field experiments. , 2008, The New phytologist.

[90]  Muhammad Ali Amer,et al.  Genome-wide association study of 107 phenotypes in a common set of Arabidopsis thaliana inbred lines , 2010, Nature.

[91]  M. Purugganan,et al.  Complex rearrangements lead to novel chimeric gene fusion polymorphisms at the Arabidopsis thaliana MAF2-5 flowering time gene cluster. , 2008, Molecular biology and evolution.

[92]  Loretta C. Johnson,et al.  Ecological genomics: understanding gene and genome function in the natural environment , 2008, Heredity.

[93]  N. Roosens,et al.  Using Arabidopsis to explore zinc tolerance and hyperaccumulation. , 2008, Trends in plant science.

[94]  T. Mackay,et al.  Heterogeneous selection at specific loci in natural environments in Arabidopsis thaliana. , 2003, Genetics.

[95]  M. Purugganan,et al.  Epistatic interaction between Arabidopsis FRI and FLC flowering time genes generates a latitudinal cline in a life history trait. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[96]  M. Daly,et al.  Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer , 2010, PLoS genetics.

[97]  Mark G. M. Aarts,et al.  What Has Natural Variation Taught Us about Plant Development, Physiology, and Adaptation? , 2009, The Plant Cell Online.

[98]  P. Hooykaas,et al.  Cre/lox-mediated site-specific integration of Agrobacterium T-DNA in Arabidopsis thaliana by transient expression of cre , 1998, Plant Molecular Biology.

[99]  P. Nilsson,et al.  Evidence for an Evolutionary History of Overcompensation in the Grassland Biennial Gentianella Campestris (Gentianaceae) , 1997, The American Naturalist.

[100]  Thomas Mitchell-Olds,et al.  Evolutionary dynamics of an Arabidopsis insect resistance quantitative trait locus , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[101]  D. Egli.  Seed- Fill Duration and Yield of Grain Crops * * Published with the approval of the Director of the Kentucky Agricultural Station Experiment Station, University of Kentucky, Lexington, Kentucky as paper number 03-06-107. , 2004 .

[102]  X. Reboud,et al.  Delaying weed adaptation to herbicide by environmental heterogeneity: a simulation approach. , 2008, Pest management science.

[103]  David L Stern,et al.  Is Genetic Evolution Predictable? , 2009, Science.

[104]  S. Vignieri,et al.  THE SELECTIVE ADVANTAGE OF CRYPSIS IN MICE , 2010, Evolution; international journal of organic evolution.

[105]  H. Kang,et al.  Variance component model to account for sample structure in genome-wide association studies , 2010, Nature Genetics.

[106]  M. Purugganan,et al.  The Genetic Architecture of Shoot Branching in Arabidopsis thaliana: A Comparative Assessment of Candidate Gene Associations vs. Quantitative Trait Locus Mapping , 2007, Genetics.

[107]  R. Mott,et al.  A Multiparent Advanced Generation Inter-Cross to Fine-Map Quantitative Traits in Arabidopsis thaliana , 2009, PLoS genetics.

[108]  R. Lister,et al.  Next is now: new technologies for sequencing of genomes, transcriptomes, and beyond. , 2009, Current opinion in plant biology.

[109]  A. González-Neira,et al.  Mouse Genome-Wide Association Mapping Needs Linkage Analysis to Avoid False-Positive Loci , 2009, PLoS genetics.

[110]  C. Fenster,et al.  Quantitative trait locus analyses and the study of evolutionary process , 2004, Molecular ecology.

[111]  Mattias Jakobsson,et al.  The Pattern of Polymorphism in Arabidopsis thaliana , 2005, PLoS biology.

[112]  E. Richards.  Inherited epigenetic variation — revisiting soft inheritance , 2006, Nature Reviews Genetics.

[113]  D. Schluter,et al.  Adaptation from standing genetic variation. , 2008, Trends in ecology & evolution.

[114]  J. Botto,et al.  Seasonal and plant-density dependency for quantitative trait loci affecting flowering time in multiple populations of Arabidopsis thaliana. , 2007, Plant, cell & environment.

[115]  J. Rafalski,et al.  Association genetics in crop improvement. , 2010, Current opinion in plant biology.

[116]  E. Xing,et al.  Statistical Estimation of Correlated Genome Associations to a Quantitative Trait Network , 2009, PLoS genetics.

[117]  M. Purugganan,et al.  A latitudinal cline in flowering time in Arabidopsis thaliana modulated by the flowering time gene FRIGIDA. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[118]  G. Mani.  Evolution of resistance in the presence of two insecticides. , 1985, Genetics.

[119]  M. Gore,et al.  Status and Prospects of Association Mapping in Plants , 2008 .

[120]  Detlef Weigel,et al.  Natural allelic variation underlying a major fitness tradeoff in Arabidopsis thaliana , 2010, Nature.

[121]  Trudy F C Mackay,et al.  Genotype-environment interactions at quantitative trait loci affecting inflorescence development in Arabidopsis thaliana. , 2003, Genetics.

[122]  J. Bennetzen,et al.  The Wheat VRN2 Gene Is a Flowering Repressor Down-Regulated by Vernalization , 2004, Science.

[123]  O. Loudet,et al.  Quantitative trait loci analysis of water and anion contents in interaction with nitrogen availability in Arabidopsis thaliana. , 2003, Genetics.

[124]  Dominique C Bergmann,et al.  From molecule to model, from environment to evolution: an integrated view of growth and development. , 2010, Current opinion in plant biology.

[125]  Peter J. Bradbury,et al.  The Genetic Architecture of Maize Flowering Time , 2009, Science.

[126]  K. Gardner,et al.  Shared quantitative trait loci underlying the genetic correlation between continuous traits , 2007, Molecular ecology.

[127]  T. Juenger,et al.  QUANTITATIVE TRAIT LOCI AFFECTING δ13C AND RESPONSE TO DIFFERENTIAL WATER AVAILIBILITY IN ARABIDOPSIS THALLANA , 2005, Evolution; international journal of organic evolution.

[128]  Holly M. Mortensen,et al.  Convergent adaptation of human lactase persistence in Africa and Europe , 2007, Nature Genetics.

[129]  G. Bell,et al.  Experimental evolution in Chlamydomonas. IV. Selection in environments that vary through time at different scales , 1998, Heredity.

[130]  M. McMullen,et al.  Genetic Properties of the Maize Nested Association Mapping Population , 2009, Science.

[131]  B. Schaal,et al.  Genetic variation for disease resistance and tolerance among Arabidopsis thaliana accessions , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[132]  Frank Johannes,et al.  Assessing the Impact of Transgenerational Epigenetic Variation on Complex Traits , 2009, PLoS genetics.

[133]  Bernd Rinn,et al.  Probing the Reproducibility of Leaf Growth and Molecular Phenotypes: A Comparison of Three Arabidopsis Accessions Cultivated in Ten Laboratories1[W] , 2010, Plant Physiology.

[134]  C. Hermans,et al.  Molecular mechanisms of metal hyperaccumulation in plants. , 2009, The New phytologist.

[135]  M. Koornneef,et al.  Naturally occurring genetic variation in Arabidopsis thaliana. , 2004, Annual review of plant biology.

[136]  M. Purugganan,et al.  Candidate Gene Association Mapping of Arabidopsis Flowering Time , 2009, Genetics.

[137]  P. Goldsbrough,et al.  Heterogeneous inbred family (HIF) analysis: a method for developing near-isogenic lines that differ at quantitative trait loci , 1997, Theoretical and Applied Genetics.

[138]  PLASTICITY TO LIGHT CUES AND RESOURCES IN ARABIDOPSIS THALIANA: TESTING FOR ADAPTIVE VALUE AND COSTS , 2000, Evolution; international journal of organic evolution.

[139]  Detlef Weigel,et al.  The Scale of Population Structure in Arabidopsis thaliana , 2010, PLoS genetics.

[140]  E. Stahl,et al.  Dynamics of disease resistance polymorphism at the Rpm1 locus of Arabidopsis , 1999, Nature.

[141]  Measuring spatial variation in natural selection using randomly‐sown seeds of Arabidopsis thaliana , 1996 .

[142]  J. Chory,et al.  Genomics tools for QTL analysis and gene discovery. , 2004, Current opinion in plant biology.

[143]  H. Ellegren,et al.  Genetic basis of fitness differences in natural populations , 2008, Nature.

[144]  R. Lister,et al.  Highly Integrated Single-Base Resolution Maps of the Epigenome in Arabidopsis , 2008, Cell.

[145]  Keyan Zhao,et al.  Genome-Wide Association Mapping in Arabidopsis Identifies Previously Known Flowering Time and Pathogen Resistance Genes , 2005, PLoS genetics.

[146]  N. Warthmann,et al.  Local-Scale Patterns of Genetic Variability, Outcrossing, and Spatial Structure in Natural Stands of Arabidopsis thaliana , 2010, PLoS genetics.

[147]  P. Insel,et al.  A Single Amino Acid Mutation Contributes to Adaptive Beach Mouse Color Pattern , 2006, Science.

[148]  Detlef Weigel,et al.  QTL Mapping in New Arabidopsis thaliana Advanced Intercross-Recombinant Inbred Lines , 2009, PloS one.

[149]  Detlef Weigel,et al.  Recombination and linkage disequilibrium in Arabidopsis thaliana , 2007, Nature Genetics.

[150]  G. Bell.  Fluctuating selection: the perpetual renewal of adaptation in variable environments , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[151]  O. Loudet,et al.  Quantitative Trait Loci Mapping in Five New Large Recombinant Inbred Line Populations of Arabidopsis thaliana Genotyped With Consensus Single-Nucleotide Polymorphism Markers , 2008, Genetics.

[152]  Thomas Mitchell-Olds,et al.  Genetic architecture of plastic methyl jasmonate responses in Arabidopsis thaliana. , 2002, Genetics.

[153]  J. Schmitt,et al.  Environmental and genetic influences on the germination of Arabidopsis thaliana in the field. , 2005 .

[154]  R. Levins.  Evolution in Changing Environments , 1968 .

[155]  E. Stahl,et al.  Genetic variation within and among populations of Arabidopsis thaliana. , 1998, Genetics.

[156]  J. Lynch,et al.  Delayed reproduction in Arabidopsis thaliana improves fitness in soil with suboptimal phosphorus availability. , 2008, Plant, cell & environment.

[157]  J. Bergelson,et al.  Impact of Initial Pathogen Density on Resistance and Tolerance in a Polymorphic Disease Resistance Gene System in Arabidopsis thaliana , 2010, Genetics.

[158]  J. Hermisson,et al.  Adaptation of a Quantitative Trait to a Moving Optimum , 2007, Genetics.