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Epistasis and balanced polymorphism influencing complex trait variation

Abstract

Complex traits such as human disease, growth rate, or crop yield are polygenic, or determined by the contributions from numerous genes in a quantitative manner. Although progress has been made in identifying major quantitative trait loci (QTL), experimental constraints have limited our knowledge of small-effect QTL, which may be responsible for a large proportion of trait variation1,2,3. Here, we identified and dissected a one-centimorgan chromosome interval in Arabidopsis thaliana without regard to its effect on growth rate, and examined the signature of historical sequence polymorphism among Arabidopsis accessions. We found that the interval contained two growth rate QTL within 210 kilobases. Both QTL showed epistasis; that is, their phenotypic effects depended on the genetic background. This amount of complexity in such a small area suggests a highly polygenic architecture of quantitative variation, much more than previously documented4. One QTL was limited to a single gene. The gene in question displayed a nucleotide signature indicative of balancing selection, and its phenotypic effects are reversed depending on genetic background. If this region typifies many complex trait loci, then non-neutral epistatic polymorphism may be an important contributor to genetic variation in complex traits.

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Figure 1: Growth rate differences between Col-0 and Ler-0 alleles in a 210-kb region of the Arabidopsis genome.
Figure 2: Fine map of the growth rate QTL downstream of the MAM cluster.
Figure 3: Fine map of the growth rate QTL upstream of the MAM cluster.

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Acknowledgements

We thank S. Donnerhacke, D. Schnabelrauch, K. Eberhardt, K. Jünemann and A. Hirsch for help with plant care and technical assistance. This work was supported by the Max Planck Society, the DFG and the European Union.

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Correspondence to Juergen Kroymann.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Methods

Describes QTL mapping with near-isogenic lines, Genotyping of advanced crosses, and Sequence Survey of the At5g23170 region from 31 Arabidopsis accessions. Also contains EMBL accession numbers for sequences from Arabidopsis accessions used in the study. (DOC 29 kb)

Supplementary Table S1

Details the PCR primer pairs used for genotyping. (DOC 53 kb)

Supplementary Figure S1

Shows Col-0 and Ler-0 At5g23170 nucleotide and amino acid alignments. (DOC 36 kb)

Supplementary Figure S2

Shows At5g23170 nucleotide polymorphisms among 31 Arabidopsis accessions. (DOC 40 kb)

Supplementary Data 1

Gives raw data for dry weight determination from near-isogenic lines. (XLS 85 kb)

Supplementary Data 2

Contains genotype and phenotype data for near-isogenic lines used for QTL mapping. (XLS 106 kb)

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Kroymann, J., Mitchell-Olds, T. Epistasis and balanced polymorphism influencing complex trait variation. Nature 435, 95–98 (2005). https://doi.org/10.1038/nature03480

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