Elucidating the Path from Genotype to Behavior in Honey Bees: Insights from Epigenomics

  • Ryszard Maleszka


One of the key unresolved issues in biology is the relationship between a limited number of genes and virtually unlimited behavioral and phenotypic complexity of organisms belonging to different phyla. Recent advances in epigenetics suggest that genomic modifications via DNA methylation provide the level of flexibility that is important for generating morphological and behavioral diversity from the same genome that might be of particular importance for post-mitotic neurons. This robust and reversible chemical modification has the capacity of creating cell-specific epigenetic signatures that can persist even in the absence of the original stimulus because of the self-perpetuating properties of the DNA methylation system. These long-lasting effects are essential to maintaining cellular memory of context-dependent patterns of transcriptional activity. The critical contribution of DNA methylation to development and brain plasticity has already been demonstrated in mammals and in honey bees. Like humans, the honey bees utilize a conserved family of enzymes called DNA methyltransferases (DNMTs) to mark their genes with methyl tags and are capable of producing highly plastic outcomes from a static genome. The honey bee offers an easily manageable and ecologically applicable model for studying the role of epigenetic mechanisms in development and behavior. The incorporation of epigenomic technologies into behavioral studies in honey bees is likely to accelerate the lingering process of translating the raw genomic sequences into a relevant neurobiological knowledge.


Royal Jelly Gene Body Methylation Standard Genetic Program Royal Jelly Protein Active Zone Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





DNA methyltransferases


Long-term memory


non-protein-coding RNAs


RNA interference


Short-term memory


  1. 1.
    Ball MP et al (2009) Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol 27(4):361–368CrossRefGoogle Scholar
  2. 2.
    Barchuk AR, Cristino AS, Kucharski R, Costa LF, Simoes ZL et al (2007) Molecular determinants of caste differentiation in the highly eusocial honeybee Apis mellifera. BMC Dev Biol 7:70PubMedCrossRefGoogle Scholar
  3. 3.
    Bullock TH, Horridge GA (1965) Structure and function in the nervous systems of invertebrates. A Series of books in biology. W. H. Freeman, San Francisco/LondonGoogle Scholar
  4. 4.
    Cedar H, Bergman Y (2009) Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 10(5):295–304PubMedCrossRefGoogle Scholar
  5. 5.
    Crick F (1984) Memory and molecular turnover. Nature 312(5990):101PubMedCrossRefGoogle Scholar
  6. 6.
    Das S, Yu LH, Gaitatzes C, Rogers R, Freeman J et al (1997) Biology’s new Rosetta stone. Nature 385(6611):29–30PubMedCrossRefGoogle Scholar
  7. 7.
    Dingman W, Sporn MB (1964) Molecular theories of memory – any theory of memory in nervous system must consider structure  +  function in entire neuron. Science 144(361):26–29PubMedCrossRefGoogle Scholar
  8. 8.
    Foret S, Kucharski R, Pittelkow Y, Lockett GA, Maleszka R (2009) Epigenetic regulation of the honey bee transcriptome: unravelling the nature of methylated genes. BMC Genomics 10:472PubMedCrossRefGoogle Scholar
  9. 9.
    Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL et al (2006) Methylation of tRNA(AsP) by the DNA methyltransferase homolog Dnmt2. Science 311(5759):395–398PubMedCrossRefGoogle Scholar
  10. 10.
    Gottlieb G (1998) Normally occurring environmental and behavioral influences on gene activity: from central dogma to probabilistic epigenesis. Psychol Rev 105(4):792–802PubMedCrossRefGoogle Scholar
  11. 11.
    Gottlieb G (2007) Probabilistic epigenesis. Dev Sci 10(1):1–11PubMedCrossRefGoogle Scholar
  12. 12.
    Greenspan RJ (2001) The flexible genome. Nat Rev Genet 2(5):383–387PubMedCrossRefGoogle Scholar
  13. 13.
    Hojo M, Kagami T, Sasaki T, Nakamura J, Sasaki M (2010) Reduced expression of major royal jelly protein 1 gene in the mushroom bodies of worker honeybees with reduced learning ability. Apidologie 41(2):194–202CrossRefGoogle Scholar
  14. 14.
    Holliday R (1999) Is there an epigenetic component in long-term memory? J Theor Biol 200(3):339–341PubMedCrossRefGoogle Scholar
  15. 15.
    Hyden H (1968) Biochemical approaches to learning and memory. In: Koestler A, Smythies JR (eds) The Alpbach Symposium 1968. Beyond reductionism, New perspectives in the life sciences. Hutchinson, LondonGoogle Scholar
  16. 16.
    Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33(Suppl):245–254PubMedCrossRefGoogle Scholar
  17. 17.
    Kucharski R, Maleszka R, Hayward DC, Ball EE (1998) A royal jelly protein is expressed in a subset of Kenyon cells in the mushroom bodies of the honey bee brain. Naturwissenschaften 85(7):343–346PubMedCrossRefGoogle Scholar
  18. 18.
    Kucharski R, Maleszka J, Foret S, Maleszka R (2008) Nutritional control of reproductive status in honeybees via DNA methylation. Science 319(5871):1827–1830PubMedCrossRefGoogle Scholar
  19. 19.
    Lockett GA, Wilkes F, Maleszka R (2010) Brain plasticity, memory and neurological disorders: an epigenetic perspective. Neuroreport 21(14):909–913PubMedCrossRefGoogle Scholar
  20. 20.
    Lyko F, Foret S, Kucharski R, Wolf S, Falckenhayn C et al (2010) The honey bee epigenomes: differential methylation of brain DNA in queens and workers. PLoS Biol 8(11):e1000506PubMedCrossRefGoogle Scholar
  21. 21.
    Maleszka R (2008) Epigenetic integration of environmental and genomic signals in honey bees. Epigenetics 3(4):188–192PubMedCrossRefGoogle Scholar
  22. 22.
    Maleszka R, Maleszka J, Barron AB, Helliwell PG (2009) Effect of age, behaviour and social environment on honey bee brain plasticity. J Comp Physiol A 195(8):733–740PubMedCrossRefGoogle Scholar
  23. 23.
    Markram H (2007) Bioinformatics - Industrializing neuroscience. Nature 445(7124):160–161PubMedCrossRefGoogle Scholar
  24. 24.
    Mattick JS, Amaral PP, Dinger ME, Mercer TR, Mehler MF (2009) RNA regulation of epigenetic processes. Bioessays 31(1):51–59PubMedCrossRefGoogle Scholar
  25. 25.
    Mattick JS, Taft RJ, Faulkner GJ (2010) A global view of genomic information - moving beyond the gene and the master regulator. Trends Genet 26(1):21–28PubMedCrossRefGoogle Scholar
  26. 26.
    Menzel R (2001) Searching for the memory trace in a mini-brain, the honeybee. Learn Mem 8(2):53–62PubMedCrossRefGoogle Scholar
  27. 27.
    Miklos GLG (1993) Molecules and cognition - the latterday lessons of levels, language, and Lac - evolutionary overview of brain structure and function in some vertebrates and invertebrates. J Neurobiol 24(6):842–890PubMedCrossRefGoogle Scholar
  28. 28.
    Miklos GL, Maleszka R (2000) Deus ex genomix. Nat Neurosci 3(5):424–425PubMedCrossRefGoogle Scholar
  29. 29.
    Miklos GL, Maleszka R (2001) Protein functions and biological contexts. Proteomics 1(2):169–178PubMedCrossRefGoogle Scholar
  30. 30.
    Miklos GLG, Maleszka R (2011) Epigenomic communication systems in humans and honey bees: from molecules to behavior. Horm Behav 59(3):399–406CrossRefGoogle Scholar
  31. 31.
    Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53(6):857–869PubMedCrossRefGoogle Scholar
  32. 32.
    Nadeau JH, Grant PL, Mankala S, Reiner AH, Richardson JE et al (1995) A Rosetta stone of mammalian genetics. Nature 373(6512):363–365PubMedCrossRefGoogle Scholar
  33. 33.
    Pennisi E (2003) Human genome. A low number wins the GeneSweep Pool. Science 300(5625):1484PubMedCrossRefGoogle Scholar
  34. 34.
    Qureshi IA, Mattick JS, Mehler MF (2010) Long non-coding RNAs in nervous system function and disease. Brain Res 1338:20–35PubMedCrossRefGoogle Scholar
  35. 35.
    Simmen MW, Leitgeb S, Clark VH, Jones SJ, Bird A (1998) Gene number in an invertebrate chordate, Ciona intestinalis. Proc Natl Acad Sci USA 95(8):4437–4440PubMedCrossRefGoogle Scholar
  36. 36.
    Sweatt JD (2009) Experience-dependent epigenetic modifications in the central nervous system. Biol Psychiatry 65(3):191–197PubMedCrossRefGoogle Scholar
  37. 37.
    Thaker HM, Kankel DR (1992) Mosaic analysis gives an estimate of the extent of genomic involvement in the development of the visual system in Drosophila melanogaster. Genetics 131(4):883–894PubMedGoogle Scholar
  38. 38.
    Tully T, Preat T, Boynton SC, Del Vecchio M (1994) Genetic dissection of consolidated memory in Drosophila. Cell 79(1):35–47PubMedCrossRefGoogle Scholar
  39. 39.
    Wang Y, Jorda M, Jones PL, Maleszka R, Ling X et al (2006) Functional CpG methylation system in a social insect. Science 314(5799):645–647PubMedCrossRefGoogle Scholar
  40. 40.
    Zemach A, McDaniel IE, Silva P, Zilberman D (2010) Genome-wide evolutionary analysis of eukaryotic DNA methylation. Science 328(5980):916–919PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Research School of BiologyThe Australian National UniversityCanberraAustralia

Personalised recommendations