Skip to main content

Thank you for visiting 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.

Genome-wide non-mendelian inheritance of extra-genomic information in Arabidopsis


A fundamental tenet of classical mendelian genetics is that allelic information is stably inherited from one generation to the next, resulting in predictable segregation patterns of differing alleles1. Although several exceptions to this principle are known, all represent specialized cases that are mechanistically restricted to either a limited set of specific genes (for example mating type conversion in yeast2) or specific types of alleles (for example alleles containing transposons3 or repeated sequences4). Here we show that Arabidopsis plants homozygous for recessive mutant alleles of the organ fusion gene HOTHEAD5 (HTH) can inherit allele-specific DNA sequence information that was not present in the chromosomal genome of their parents but was present in previous generations. This previously undescribed process is shown to occur at all DNA sequence polymorphisms examined and therefore seems to be a general mechanism for extra-genomic inheritance of DNA sequence information. We postulate that these genetic restoration events are the result of a template-directed process that makes use of an ancestral RNA-sequence cache.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


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

Figure 1: Molecular genetic analysis of HTH.
Figure 2: DNA sequences of HTH and HTL genes around the sites of mutation in hth-4, hth-8 and hth-10.


  1. Mendel, G. Versuche über Pflanzen Hybriden. Verhandl. Naturforsch. Ver. Brünn 4, 3–47 (1866)

    Google Scholar 

  2. Klar, A. J., Fogel, S. & Lusnak, K. Gene conversion of the mating-type locus in Saccharomyces cerevisiae . Genetics 92, 777–782 (1979)

    CAS  PubMed  PubMed Central  Google Scholar 

  3. McClintock, B. The origin and behavior of mutable loci in maize. Proc. Natl Acad. Sci. USA 36, 344–355 (1950)

    Article  ADS  CAS  Google Scholar 

  4. Gondo, Y. et al. High-frequency genetic reversion mediated by a DNA duplication: the mouse pink-eyed unstable mutation. Proc. Natl Acad. Sci. USA 90, 297–301 (1993)

    Article  ADS  CAS  Google Scholar 

  5. Lolle, S. J., Hsu, W. & Pruitt, R. E. Genetic analysis of organ fusion in Arabidopsis thaliana . Genetics 149, 607–619 (1998)

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Krolikowski, K. A., Victor, J. L., Nussbaum Wagler, T., Lolle, S. J. & Pruitt, R. E. Isolation and characterization of the Arabidopsis organ fusion gene HOTHEAD . Plant J. 35, 501–511 (2003)

    Article  CAS  Google Scholar 

  7. Song, K., Lu, P., Tang, K. & Osborn, T. C. Rapid genome change in synthetic polyploids of Brassica and its implications for polyploid evolution. Proc. Natl Acad. Sci. USA 92, 7719–7723 (1995)

    Article  ADS  CAS  Google Scholar 

  8. Taller, J., Hirata, Y., Yagishita, N., Kita, M. & Ogata, S. Graft-induced genetic changes and the inheritance of several characteristics in pepper (Capsicum annuum L.). Theor. Appl. Genet. 97, 705–713 (1998)

    Article  CAS  Google Scholar 

  9. Auerbach, C. & Kilbey, B. J. Mutation in eukaryotes. Annu. Rev. Genet. 5, 163–218 (1971)

    Article  CAS  Google Scholar 

  10. Fire, A. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans . Nature 391, 806–811 (1998)

    Article  ADS  CAS  Google Scholar 

  11. Cogoni, C. et al. Transgene silencing of the al-1 gene in vegetative cells of Neurospora is mediated by a cytoplasmic effector and does not depend on DNA-DNA interactions or DNA methylation. EMBO J. 15, 3153–3163 (1996)

    Article  CAS  Google Scholar 

  12. Palauqui, J. C., Elmayan, T., Pollien, J. M. & Vaucheret, H. Systemic acquired silencing: transgene-specific post-transcriptional silencing is transmitted by grafting from silenced stocks to non-silenced scions. EMBO J. 16, 4738–4745 (1997)

    Article  CAS  Google Scholar 

  13. Cogoni, C. & Macino, G. Gene silencing in Neurospora crassa requires a protein homologous to RNA-dependent RNA polymerase. Nature 399, 166–169 (1999)

    Article  ADS  CAS  Google Scholar 

  14. Dalmay, T., Hamilton, A., Rudd, S., Angell, S. & Baulcombe, D. C. An RNA-dependent RNA polymerase gene in Arabidopsis is required for posttranscriptional gene silencing mediated by a transgene but not by a virus. Cell 101, 543–553 (2000)

    Article  CAS  Google Scholar 

  15. Mourrain, P. et al. Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance. Cell 101, 533–542 (2000)

    Article  CAS  Google Scholar 

  16. Wassenegger, M., Heimes, S., Riedel, L. & Sanger, H. L. RNA-directed de novo methylation of genomic sequences in plants. Cell 76, 567–576 (1994)

    Article  CAS  Google Scholar 

  17. Mette, M. F., Aufsatz, W., van der Winden, J., Matzke, M. A. & Matzke, A. J. Transcriptional silencing and promoter methylation triggered by double-stranded RNA. EMBO J. 19, 5194–5201 (2000)

    Article  CAS  Google Scholar 

  18. Bao, N., Lye, K.-W. & Barton, M. K. MicroRNA binding sites in Arabidopsis class III HD-ZIP mRNAs are required for methylation of the template chromosome. Dev. Cell 7, 653–662 (2004)

    Article  CAS  Google Scholar 

  19. Cole-Strauss, A. et al. Correction of the mutation responsible for sickle cell anemia by an RNA-DNA oligonucleotide. Science 273, 1386–1389 (1996)

    Article  ADS  CAS  Google Scholar 

  20. Beetham, P. R., Kipp, P. B., Sawycky, X. L., Arntzen, C. J. & May, G. D. A tool for functional plant genomics: chimeric RNA/DNA oligonucleotides cause in vivo gene-specific mutations. Proc. Natl Acad. Sci. USA 96, 8774–8778 (1999)

    Article  ADS  CAS  Google Scholar 

  21. Zhu, T. et al. Targeted manipulation of maize genes in vivo using chimeric RNA/DNA oligonucleotides. Proc. Natl Acad. Sci. USA 96, 8768–8773 (1999)

    Article  ADS  CAS  Google Scholar 

  22. Hall, B. G. Spontaneous point mutations that occur more often when advantageous than when neutral. Genetics 126, 5–16 (1990)

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Foster, P. L. & Cairns, J. Mechanisms of directed mutation. Genetics 131, 783–789 (1992)

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Galitski, T. & Roth, J. R. A search for a general phenomenon of adaptive mutability. Genetics 143, 645–659 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Ries, G. et al. Elevated UV-B radiation reduces genome stability in plants. Nature 406, 98–101 (2000)

    Article  ADS  CAS  Google Scholar 

  26. Bjedov, I. et al. Stress-induced mutagenesis in bacteria. Science 300, 1404–1409 (2003)

    Article  ADS  CAS  Google Scholar 

  27. Kovalchuk, I. et al. Pathogen-induced systemic plant signal triggers DNA rearrangements. Nature 423, 760–762 (2003)

    Article  ADS  CAS  Google Scholar 

  28. Queitsch, C., Sangster, T. A. & Lindquist, S. Hsp90 as a capacitor of phenotypic variation. Nature 417, 618–624 (2002)

    Article  ADS  CAS  Google Scholar 

  29. Rutherford, S. L. & Lindquist, S. Hsp90 as a capacitor for morphological evolution. Nature 396, 336–342 (1998)

    Article  ADS  CAS  Google Scholar 

  30. Pruitt, R. E., Vielle-Calzada, J. P., Ploense, S. E., Grossniklaus, U. & Lolle, S. J. FIDDLEHEAD, a gene required to suppress epidermal cell interactions in Arabidopsis, encodes a putative lipid biosynthetic enzyme. Proc. Natl Acad. Sci. USA 97, 1311–1316 (2000)

    Article  ADS  CAS  Google Scholar 

Download references


We thank R. M. Lee and T. Nussbaum Wagler for technical assistance, and J. A. Banks, J. L. Bowman, U. Grossniklaus, R. A. Jorgensen, J. Ogas, D. R. Smyth, A. Steimer, V. Sundaresan and M. A. Webb for discussions. This work was supported by the National Science Foundation. Any opinion, findings, conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Robert E. Pruitt.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lolle, S., Victor, J., Young, J. et al. Genome-wide non-mendelian inheritance of extra-genomic information in Arabidopsis. Nature 434, 505–509 (2005).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


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.


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