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Reversible switching between epigenetic states in honeybee behavioral subcastes


In honeybee societies, distinct caste phenotypes are created from the same genotype, suggesting a role for epigenetics in deriving these behaviorally different phenotypes. We found no differences in DNA methylation between irreversible worker and queen castes, but substantial differences between nurses and forager subcastes. Reverting foragers back to nurses reestablished methylation levels for a majority of genes and provides, to the best of our knowledge, the first evidence in any organism of reversible epigenetic changes associated with behavior.

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Figure 1: DNA methylation changes were found between nurses and foragers, but not between queens and workers.
Figure 2: DNA methylation distinguishes nurses, foragers and reverted nurses.

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  1. 1

    Ji, H. et al. Nature 467, 338–342 (2010).

    CAS  Article  Google Scholar 

  2. 2

    Wolf, C. & Linden, D.E. Genes Brain Behav. 11, 3–28 (2012).

    CAS  Article  Google Scholar 

  3. 3

    Wang, Y. et al. Science 314, 645–647 (2006).

    CAS  Article  Google Scholar 

  4. 4

    Winston, M.L. The Biology of the Honey Bee (Harvard University Press, 1987).

  5. 5

    Whitfield, C.W. Science 302, 296–299 (2003).

    CAS  Article  Google Scholar 

  6. 6

    Robinson, G.E., Page, R.E., Strambi, C. & Strambi, A. Ethology 90, 336–348 (1992).

    CAS  Article  Google Scholar 

  7. 7

    Elango, N., Hunt, B.G., Goodisman, M.A. & Yi, S.V. Proc. Natl. Acad. Sci. USA 106, 11206–11211 (2009).

    CAS  Article  Google Scholar 

  8. 8

    Lyko, F. et al. PLoS Biol. 8, e1000506 (2010).

    Article  Google Scholar 

  9. 9

    Suganuma, T. et al. Nat. Struct. Mol. Biol. 15, 364–372 (2008).

    CAS  Article  Google Scholar 

  10. 10

    Tsukiyama, T., Daniel, C., Tamkun, J. & Wu, C. Cell 83, 1021–1026 (1995).

    CAS  Article  Google Scholar 

  11. 11

    Barak, O. et al. EMBO J. 22, 6089–6100 (2003).

    CAS  Article  Google Scholar 

  12. 12

    Terriente-Félix, A., Molnar, C., Gómez-Skarmeta, J.L. & de Celis, J.F. Dev. Biol. 350, 382–392 (2011).

    Article  Google Scholar 

  13. 13

    Melicharek, D.J., Ramirez, L.C., Singh, S., Rhea, T. & Marenda, D.R. Hum. Mol. Genet. 19, 4253–4264 (2010).

    CAS  Article  Google Scholar 

  14. 14

    Amdam, G.V. Aging Cell 10, 18–27 (2011).

    CAS  Article  Google Scholar 

  15. 15

    Goldman-Levi, R., Miller, C., Bogoch, J. & Zak, N.B. Nucleic Acids Res. 24, 3121–3128 (1996).

    CAS  Article  Google Scholar 

  16. 16

    Linder, P. Nucleic Acids Res. 34, 4168–4180 (2006).

    CAS  Article  Google Scholar 

  17. 17

    Parsyan, A. et al. Nat. Rev. Mol. Cell Biol. 12, 235–245 (2011).

    CAS  Article  Google Scholar 

  18. 18

    Guo, J.U. et al. Nat. Neurosci. 14, 1345–1351 (2011).

    CAS  Article  Google Scholar 

  19. 19

    Miller, C.A. & Sweatt, J.D. Neuron 53, 857–869 (2007).

    CAS  Article  Google Scholar 

  20. 20

    Weaver, I.C. et al. Nat. Neurosci. 7, 847–854 (2004).

    CAS  Article  Google Scholar 

  21. 21

    Amdam, G.V. et al. Exp. Gerontol. 40, 939–947 (2005).

    CAS  Article  Google Scholar 

  22. 22

    Page, R.E. & Fondrk, M.K. Behav. Ecol. Sociobiol. 36, 135–144 (1995).

    Article  Google Scholar 

  23. 23

    Laidlaw, H.H. & Page, R.E. Queen Rearing and Bee Breeding (Wicwas Press, 1997).

  24. 24

    Aryee, M.J. et al. Biostatistics 12, 197–210 (2011).

    Article  Google Scholar 

  25. 25

    Irizarry, R.A. et al. Genome Res. 18, 780–790 (2008).

    CAS  Article  Google Scholar 

  26. 26

    Huang, D.W., Sherman, B.T. & Lempicki, R.A. Nat. Protoc. 4, 44–57 (2009).

    CAS  Article  Google Scholar 

  27. 27

    Hansen, K.D. et al. Nat. Genet. 43, 768–775 (2011).

    CAS  Article  Google Scholar 

  28. 28

    Lister, R. et al. Nature 462, 315–322 (2009).

    CAS  Article  Google Scholar 

  29. 29

    Langmead, B. & Salzberg, S.L. Nat. Methods 9, 357–359 (2012).

    CAS  Article  Google Scholar 

  30. 30

    Trapnell, C., Pachter, L. & Salzberg, S.L. Bioinformatics 25, 1105–1111 (2009).

    CAS  Article  Google Scholar 

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We thank E. Fennern, N. Baker, K. Flores and O. Kaftanoglu for assistance with colonies, bees and brain dissections, and A. Doi for reviewing the manuscript. We thank G. Klein for serving as scientific schadchen to A.P.F. and G.V.A. after hearing them lecture on different occasions at I. Ernberg's “What is Life” series at the Karolinska Institute, without which this research would not have taken place. G.V.A. was funded by the Research Council of Norway #191699 and the PEW Charitable Trust #2009-000068-001. A.P.F. was funded by US National Institutes of Health grant 1DP1OD008324.

Author information




B.R.H. performed genome-scale, gene-specific DNA methylation analysis and performed gene expression analysis. F.W. raised bees and manipulated hives for reversion experiment, and collected bees and dissected brains. R.I., M.J.A., K.D.H., B.L. and B.R.H. performed statistical analysis. B.R.H. and M.J.A. generated microarray data sets. B.R.H., B.L. and K.D.H. generated WGBS and RNAseq data sets. A.P.F. and G.V.A. conceived, designed and oversaw the experiments. A.P.F., B.R.H. and G.V.A. wrote the paper with the assistance of K.D.H., M.J.A., B.L. and F.W.

Corresponding authors

Correspondence to Gro V Amdam or Andrew P Feinberg.

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The authors declare no competing financial interests.

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Herb, B., Wolschin, F., Hansen, K. et al. Reversible switching between epigenetic states in honeybee behavioral subcastes. Nat Neurosci 15, 1371–1373 (2012).

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