Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Epistasis and balanced polymorphism influencing complex trait variation

Nature volume 435, pages 95–98 (2005)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Lohmueller, K. E., Pearce, C. L., Pike, M., Lander, E. S. & Hirschhorn, J. N. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nature Genet. 33, 177–182 (2003)

    Article  CAS  PubMed  Google Scholar 

  2. Mackay, T. F. C. The genetic architecture of quantitative traits: lessons from Drosophila. Curr. Opin. Genet. Dev. 14, 253–257 (2004)

    Article  CAS  PubMed  Google Scholar 

  3. Steinmetz, L. M. et al. Dissecting the architecture of a quantitative trait locus in yeast. Nature 416, 326–330 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Koornneef, M., Alonso-Blanco, C. & Vreugdenhill, D. Naturally occurring genetic variation in Arabidopsis thaliana. Annu. Rev. Plant Biol. 55, 141–172 (2004)

    Article  CAS  PubMed  Google Scholar 

  5. Dilda, C. L. & Mackay, T. F. C. The genetic architecture of Drosophila sensory bristle number. Genetics 162, 1655–1674 (2002)

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Kroymann, J. et al. A gene controlling variation in Arabidopsis thaliana glucosinolate composition is part of the methionine chain elongation pathway. Plant Physiol. 127, 1077–1088 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kroymann, J., Donnerhacke, S., Schnabelrauch, D. & Mitchell-Olds, T. Evolutionary dynamics of an Arabidopsis insect resistance QTL. Proc. Natl Acad. Sci. USA 100, 14587–14592 (2003)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lister, C. & Dean, C. Recombinant inbred lines for mapping RFLP and phenotypic markers. Plant J. 4, 745–750 (1993)

    Article  CAS  Google Scholar 

  9. Becraft, P. W., Stinard, P. S. & McCarty, D. R. CRINKLY4: a receptor kinase with TNFR similarity, involved in maize epidermal differentiation. Science 273, 1406–1409 (1996)

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Shiu, S. H. & Bleecker, A. B. Receptor-like kinases from Arabidopsis form a monophyletic gene family related to animal receptor kinases. Proc. Natl Acad. Sci. USA 98, 10763–10768 (2001)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Becraft, P. W. Receptor kinase signaling in plant development. Annu. Rev. Cell Dev. Biol. 18, 163–192 (2002)

    Article  CAS  PubMed  Google Scholar 

  12. Zhou, J., Loh, Y. T., Bressan, R. A. & Martin, G. B. The tomato gene Pti1 encodes a serine/threonine kinase that is phosphorylated by Pto and is involved in the hypersensitive response. Cell 83, 925–935 (1995)

    Article  CAS  PubMed  Google Scholar 

  13. Wright, S. I., Lauga, B. & Charlesworth, D. Rates and patterns of molecular evolution in inbred and outbred Arabidopsis. Mol. Biol. Evol. 19, 1407–1420 (2002)

    Article  CAS  PubMed  Google Scholar 

  14. Tian, D., Araki, H., Stahl, E., Bergelson, J. & Kreitman, M. Signature of balancing selection in Arabidopsis. Proc. Natl Acad. Sci. USA 99, 11525–11530 (2002)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tajima, F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123, 585–595 (1989)

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Schmid, K. J., Ramos-Onsins, S., Ringys-Beckstein, H., Weisshaar, B. & Mitchell-Olds, T. A multilocus sequence survey in Arabidopsis thaliana reveals a genome-wide departure from a neutral model of DNA sequence polymorphism. Genetics 169, 1601–1615 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Haubold, B., Kroymann, J., Ratzka, A., Mitchell-Olds, T. & Wiehe, T. Recombination and gene conversion in a 170-kb genomic region of Arabidopsis thaliana. Genetics 161, 1269–1278 (2002)

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Nordborg, M. et al. The extent of linkage disequilibrium in Arabidopsis thaliana. Nature Genet. 30, 190–193 (2002)

    Article  CAS  PubMed  Google Scholar 

  19. Lauter, N. & Doebley, J. Genetic variation for phenotypically invariant traits detected in Teosinte: implications for the evolution of novel forms. Genetics 160, 333–342 (2002)

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Gibson, G. & Dworkin, I. Uncovering cryptic genetic variation. Nature Rev. Genet. 5, 681–690 (2004)

    Article  CAS  PubMed  Google Scholar 

  21. Torii, K. U. et al. The Arabidopsis ERECTA gene encodes a putative receptor protein kinase with extracellular leucine-rich repeats. Plant Cell 8, 735–746 (1996)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rozas, J., Sánchez-DelBarrio, J. C., Messeguer, X. & Rozas, R. DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics 19, 2496–2497 (2003)

    Article  CAS  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of Genetics & Evolution, Max Planck Institute for Chemical Ecology, Hans-Knoell-Str. 8, D-07745, Jena, Germany

    Juergen Kroymann & Thomas Mitchell-Olds

Authors
  1. Juergen Kroymann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Mitchell-Olds
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juergen Kroymann.

Ethics declarations

Competing interests

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)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature03480

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing