Eusocial insects as emerging models for behavioural epigenetics

Journal name:
Nature Reviews Genetics
Volume:
15,
Pages:
677–688
Year published:
DOI:
doi:10.1038/nrg3787
Published online
Corrected online

Abstract

Understanding the molecular basis of how behavioural states are established, maintained and altered by environmental cues is an area of considerable and growing interest. Epigenetic processes, including methylation of DNA and post-translational modification of histones, dynamically modulate activity-dependent gene expression in neurons and can therefore have important regulatory roles in shaping behavioural responses to environmental cues. Several eusocial insect species — with their unique displays of behavioural plasticity due to age, morphology and social context — have emerged as models to investigate the genetic and epigenetic underpinnings of animal social behaviour. This Review summarizes recent studies in the epigenetics of social behaviour and offers perspectives on emerging trends and prospects for establishing genetic tools in eusocial insects.

At a glance

Figures

  1. Epigenetic response threshold model of behavioural plasticity.
    Figure 1: Epigenetic response threshold model of behavioural plasticity.

    a | The phenotypic response of an individual to a transient environmental stimulus depends on several factors: parentally inherited factors (I), which include genotype, epigenotype and maternal factors (for example, maternal mRNA); developmental history (D) that results in its current physiological condition; and biotic and abiotic environmental factors (E). Square brackets around paternal factors indicate that, in eusocial insects, all F1 males and some F1 females do not inherit paternal factors from the P0 generation. The three primary factors (I, E and D) are integrated by an epigenetic transfer function to define a response threshold f(I, E, D) that determines an individual's sensitivity to novel environmental stimuli, which are first perceived (for example, by antennal olfactory receptors), and then transduced and 'quantified' into a signal or stimulus through intracellular signal transduction pathways (for example, by neuroendocrine pathways regulating Juvenile hormone (JH) titre (Box 3)). Only the environmental factors with an internalized signal value (s) that exceeds the response threshold value f(I, E, D) can induce stable epigenetic changes to behavioural phenotypes. In the plot, the threshold for foraging behaviour decreases with age (red dashed line). When the foraging stimulus (apple) exceeds the threshold level, the animal undergoes an epigenetic behavioural state transition from nursing (orange) to foraging (blue). b | A response threshold changes according to environmental factors (including nutrition), for example, to permit regulation of caste fate in larvae (that is, transient periods of JH sensitivity) (left panel). In many cases, the quantification of the internalized signal value (s) changes rather than the threshold itself; notably, the JH titre decreases through larval stages until it is less than the level needed to prevent pupation. A response threshold changes in adults according to changes in reproductive social context, which results in reproductive polyethism. For example, loss of existing reproductive individuals in Harpegnathos saltator induces a transition from worker to gamergate, whereas an induced loss of status leads to a reversion to worker status (right panel). c | As physiological condition is determined by the interactions between inherited factors and environmental cues, naturally occurring genetic variation (that is, allelic variation among individuals in a colony) can directly influence response thresholds, for example, by lowering the threshold for a given cue to increase environmental sensitivity (left panel). Genetic divergence may also alter response thresholds in a qualitative manner, for example, by prohibiting sensitivity to a given stimulus (for example, JH), as in the case of major caste determination in dimorphic species or supersoldiers in Pheidole sp. ants130 (right panel).

  2. Epigenetic mechanisms of gene regulation in the insect brain.
    Figure 2: Epigenetic mechanisms of gene regulation in the insect brain.

    a | The neuroendocrine system regulates gene expression in the brain by targeting transcription factors (TFs), non-coding RNAs (ncRNAs) and chromatin regulatory proteins, which involves histone post-translational modifications (PTMs) and chromatin remodelling. TFs (such as Cyclic AMP response element-binding protein (CREB)) and ncRNAs operate partly through recruitment of histone modifiers (a specific class of chromatin regulatory proteins), such as CREB-binding protein (CBP), which is a transcriptional co-activator that has histone acetyltransferase activity. In this way, signalling pathways may alter the chromatin landscape around target genes from repressive (for example, histone H3 lysine 27 trimethylation (H3K27me3; red circles)) to active (for example, H3K27 acetylation; green circles). Here, chromatin is depicted using the 'beads on a string' model, with DNA (black line) wrapped around histone octamers. b | Correlation of gene body DNA methylation with gene expression and alternative splicing is shown. At the genome-wide level, hypermethylation predominantly occurs at genes with medium to high levels of transcription. In addition, inclusion of alternatively spliced exons normally correlates with hypomethylated regions. However, in some cases, the opposite is also true, which suggests the recruitment of different factors to different gene loci38. IIS, Insulin/Insulin-like growth factor signalling; m7G, 7-methyl-guanosine cap.

  3. Genetic approaches in eusocial insects.
    Figure 3: Genetic approaches in eusocial insects.

    a | Pharmaceutical compounds and RNA interference (RNAi) are currently used to change gene expression in somatic cells to alter caste fate and behaviour in eusocial insects. b | A schematic is shown for generating mutant and transgenic lines by germline genetic manipulation in lineages of wasps, termites, bees and ants, such as Polistes metricus, Zootermopsis nevadensis, Apis mellifera, Lasioglossum albipes, Cerapachys biroi, Monomorium pharaonis and Harpegnathos saltator. With appropriate manipulation, the reproductive females in these species can either mate or be inseminated artificially to generate progeny from controlled genetic crosses, which are required for some genetic manipulations (for example, temporally controlled or tissue-specific overexpression and knockdown). Blue scale bars represent 1 mm, and black scale bars represent 5 mm. CRISPR–Cas, clustered regularly interspaced short palindromic repeat–CRISPR-associated. C. biroi image courtesy of D. Kronauer (The Rockefeller University, New York, USA); C. floridanus and Z. nevadensis images courtesy of A. Smith (University of Illinois at Urbana-Champaign, USA); H. saltator image courtesy of C. Penick (North Carolina State University, USA); L. albipes image courtesy of S. Kocher (Museum of Comparative Zoology, Massachusetts, USA); M. pharaonis image courtesy of L. Pontieri (University of Copenhagen, Denmark); P. metricus image courtesy of P. Coin (Durham, North Carolina, USA).

Change history

Corrected online 11 September 2014
The postal addresses for some of the authors' affiliations have now been corrected to "Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA"; "Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA"; and "Epigenetics Program, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA".

References

  1. Gerozissis, K. Brain insulin: regulation, mechanisms of action and functions. Cell. Mol. Neurobiol. 23, 125 (2003).
  2. Margulies, C., Tully, T. & Dubnau, J. Deconstructing memory in Drosophila. Curr. Biol. 15, R700R713 (2005).
  3. Dulac, C. Brain function and chromatin plasticity. Nature 465, 728735 (2010).
  4. Kim, J. & Eberwine, J. RNA: state memory and mediator of cellular phenotype. Trends Cell Biol. 20, 311318 (2010).
  5. Giurfa, M. & Sandoz, J. C. Invertebrate learning and memory: fifty years of olfactory conditioning of the proboscis extension response in honeybees. Learn. Mem. 19, 5466 (2012).
  6. Zayed, A. & Robinson, G. E. Understanding the relationship between brain gene expression and social behavior: lessons from the honey bee. Annu. Rev. Genet. 46, 591615 (2012).
  7. Bonasio, R. Emerging topics in epigenetics: ants, brains, and noncoding RNAs. Ann. NY Acad. Sci. 1260, 1423 (2012).
  8. Acar, M., Becskei, A. & van Oudenaarden, A. Enhancement of cellular memory by reducing stochastic transitions. Nature 435, 228232 (2005).
  9. Bonasio, R., Tu, S. & Reinberg, D. Molecular signals of epigenetic states. Science 330, 612616 (2010).
  10. Jasinska, A. J. & Freimer, N. B. The complex genetic basis of simple behavior. J. Biol. 8, 71 (2009).
  11. Takahashi, J. S., Pinto, L. H. & Vitaterna, M. H. Forward and reverse genetic approaches to behavior in the mouse. Science 264, 17241733 (1994).
  12. Nottebohm, F. The road we travelled: discovery, choreography, and significance of brain replaceable neurons. Ann. NY Acad. Sci. 1016, 628658 (2004).
  13. Raddatz, G. et al. Dnmt2-dependent methylomes lack defined DNA methylation patterns. Proc. Natl Acad. Sci. USA 110, 86278631 (2013).
  14. Crabbe, J. C., Wahlsten, D. & Dudek, B. C. Genetics of mouse behavior: interactions with laboratory environment. Science 284, 16701672 (1999).
  15. Bier, E. & McGinnis, W. in Inborn Errors of Development (eds Epstein, C. J., Erikson, R. P. & Wynshaw-Boris, A.) 2545 (Oxford Univ. Press, 2003).
  16. Hunt, G. J. Flight and fight: a comparative view of the neurophysiology and genetics of honey bee defensive behavior. J. Insect Physiol. 53, 399410 (2007).
  17. Withers, G. S., Fahrbach, S. E. & Robinson, G. E. Effects of experience and juvenile hormone on the organization of the mushroom bodies of honey bees. J. Neurobiol. 26, 130144 (1995).
  18. Gronenberg, W. The trap-jaw mechanism in the dacetine ants Daceton armigerum and Strumigenys sp. J. Exp. Biol. 199, 20212033 (1996).
  19. Ehmer, B. & Gronenberg, W. Segregation of visual input to the mushroom bodies in the honeybee (Apis mellifera). J. Comp. Neurol. 451, 362373 (2002).
  20. Ehmer, B. & Gronenberg, W. Mushroom body volumes and visual interneurons in ants: comparison between sexes and castes. J. Comp. Neurol. 469, 198213 (2004).
  21. Rossler, W. & Zube, C. Dual olfactory pathway in Hymenoptera: evolutionary insights from comparative studies. Arthropod Struct. Dev. 40, 349357 (2011).
    References 17–21 analyse brain morphology and neuronal connections, which are associated with learning and behaviour in exemplary eusocial insects.
  22. Nijhout, H. F. & Wheeler, D. E. Juvenile hormone and the physiological basis of insect polymorphisms. Q. Rev. Biol. 57, 109133 (1982).
  23. Wheeler, D. E. Developmental and physiological determinants of caste in social Hymenoptera: evolutionary implications. Am. Naturalist 128, 1334 (1986).
  24. Seeley, T. D. Honeybee Democracy (Princeton Univ. Press, 2010).
  25. Liang, Z. S. et al. Molecular determinants of scouting behavior in honey bees. Science 335, 12251228 (2012).
  26. Robinson, G. E. Regulation of division of labor in insect societies. Annu. Rev. Entomol. 37, 637665 (1992).
  27. Herb, B. R. et al. Reversible switching between epigenetic states in honeybee behavioral subcastes. Nature Neurosci. 15, 13711373 (2012).
    This is a comparative analysis of DNA methylation profiles between honeybee nurses, foragers and reverted foragers; it shows, for the first time, the evidence of reversible epigenetic changes associated with behavioural states in eusocial insects.
  28. Liebig, J., Hölldobler, B. & Peeters, C. Are ant workers capable of colony foundation? Naturwissenschaften 85, 133135 (1998).
  29. Penick, C. A., Liebig, J. & Brent, C. S. Reproduction, dominance, and caste: endocrine profiles of queens and workers of the ant Harpegnathos saltator. J. Comp. Physiol. A Neuroethol Sens. Neural Behav. Physiol. 197, 10631071 (2011).
  30. Michener, C. D. The Bees of the World (Johns Hopkins Univ. Press, 2000).
  31. Honeybee Genome Sequencing, C. Insights into social insects from the genome of the honeybee Apis mellifera. Nature 443, 931949 (2006).
    The first eusocial insect genome was analyzed in honeybees. The honeybee genome, plus the genomes of eight ant species, halictid bees and dampwood termites (reference 32–36), laid a foundation for further epigenetic analyses.
  32. Bonasio, R. et al. Genomic comparison of the ants Camponotus floridanus and Harpegnathos saltator. Science 329, 10681071 (2010).
  33. Gadau, J. et al. The genomic impact of 100 million years of social evolution in seven ant species. Trends Genet. 28, 1421 (2012).
  34. Oxley, P. R. et al. The genome of the clonal raider ant Cerapachys biroi. Curr. Biol. 24, 451458 (2014).
  35. Kocher, S. D. et al. The draft genome of a socially polymorphic halictid bee, Lasioglossum albipes. Genome Biol. 14, R142 (2013).
  36. Terrapon, N. et al. Molecular traces of alternative social organization in a termite genome. Nature Commun. 5, 3636 (2014).
  37. Lyko, F. et al. The honey bee epigenomes: differential methylation of brain DNA in queens and workers. PLoS Biol. 8, e1000506 (2010).
    This is the first brain methylome study in eusocial insects, which highlights the differentially methylated genes between reproductive and non-reproductive castes, and the potential role of DNA methylation in modulating alternative splicing.
  38. Bonasio, R. et al. Genome-wide and caste-specific DNA methylomes of the ants Camponotus floridanus and Harpegnathos saltator. Curr. Biol. 22, 17551764 (2012).
    This is the first study of DNA methyaltion in ants, which reveals several conserved characteristics in two species, including non-CpG methylation, enrichment of methylcytosine in exons, ASM and association of DNA methylation with alternative splicing.
  39. Simola, D. F. et al. Social insect genomes exhibit dramatic evolution in gene composition and regulation while preserving regulatory features linked to sociality. Genome Res. 23, 12351247 (2013).
  40. Simola, D. F. et al. A chromatin link to caste identity in the carpenter ant Camponotus floridanus. Genome Res. 23, 486496 (2013).
    This is the first study to analyse the role of histone modifications in eusocial insects, which reveals a potential regulatory role for H3K27ac and CBP in sex and worker caste differentiation.
  41. Weiner, S. A. et al. A survey of DNA methylation across social insect species, life stages, and castes reveals abundant and caste-associated methylation in a primitively social wasp. Naturwissenschaften 100, 795799 (2013).
  42. Amarasinghe, H. E., Clayton, C. I. & Mallon, E. B. Methylation and worker reproduction in the bumble-bee (Bombus terrestris). Proc. R. Soc. B 281, 20132502 (2014).
  43. Robinson, G. E., Grozinger, C. M. & Whitfield, C. W. Sociogenomics: social life in molecular terms. Nature Rev. Genet. 6, 257270 (2005).
  44. Hölldobler, B. & Wilson, E. O. The Ants (Belknap Press, 1990).
  45. Liebig, J., Peeters, C., Oldham, N. J., Markstadter, C. & Hölldobler, B. Are variations in cuticular hydrocarbons of queens and workers a reliable signal of fertility in the ant Harpegnathos saltator? Proc. Natl Acad. Sci. USA 97, 41244131 (2000).
  46. Grozinger, C. M., Sharabash, N. M., Whitfield, C. W. & Robinson, G. E. Pheromone-mediated gene expression in the honey bee brain. Proc. Natl Acad. Sci. USA 100 (Suppl. 2), 1451914525 (2003).
  47. Kamakura, M. Royalactin induces queen differentiation in honeybees. Nature 473, 478483 (2011).
  48. Liebig, J., Peeters, C. & Hölldobler, B. Worker policing limits the number of reproductives in a ponerine ant. Proc. R. Soc. B 266, 18651870 (1999).
  49. Endler, A. et al. Surface hydrocarbons of queen eggs regulate worker reproduction in a social insect. Proc. Natl Acad. Sci. USA 101, 29452950 (2004).
  50. Smith, A. A., Holldober, B. & Liebig, J. Cuticular hydrocarbons reliably identify cheaters and allow enforcement of altruism in a social insect. Curr. Biol. 19, 7881 (2009).
  51. Whitfield, C. W., Cziko, A. M. & Robinson, G. E. Gene expression profiles in the brain predict behavior in individual honey bees. Science 302, 296299 (2003).
    This pioneering genome-wide analysis reveals that gene expression profiles are closely assoicated with worker behaviours in honeybees.
  52. Toth, A. L. et al. Wasp gene expression supports an evolutionary link between maternal behavior and eusociality. Science 318, 441444 (2007).
  53. Menzel, R. The honeybee as a model for understanding the basis of cognition. Nature Rev. Neurosci. 13, 758768 (2012).
  54. Evans, J. D. & Wheeler, D. E. Gene expression and the evolution of insect polyphenisms. Bioessays 23, 6268 (2001).
  55. Borrelli, E., Nestler, E. J., Allis, C. D. & Sassone-Corsi, P. Decoding the epigenetic language of neuronal plasticity. Neuron 60, 961974 (2008).
  56. Kim, J. B. et al. Direct reprogramming of human neural stem cells by OCT4. Nature 461, 649643 (2009).
  57. Job, C. & Eberwine, J. Localization and translation of mRNA in dendrites and axons. Nature Rev. Neurosci. 2, 889898 (2001).
  58. True, H. L., Berlin, I. & Lindquist, S. L. Epigenetic regulation of translation reveals hidden genetic variation to produce complex traits. Nature 431, 184187 (2004).
  59. Sul, J. Y. et al. Transcriptome transfer produces a predictable cellular phenotype. Proc. Natl Acad. Sci. USA 106, 76247629 (2009).
  60. Page, R. E. & Fondrk, M. K. The effects of colony level selection on the social-organization of honey-bee (Apis-mellifera L) colonies - colony level components of pollen hoarding. Behav. Ecol. Sociobiol. 36, 135144 (1995).
  61. Chandrasekaran, S. et al. Behavior-specific changes in transcriptional modules lead to distinct and predictable neurogenomic states. Proc. Natl Acad. Sci. USA 108, 1802018025 (2011).
  62. Tie, F. et al. CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 136, 31313141 (2009).
  63. Graff, J. & Tsai, L. H. Histone acetylation: molecular mnemonics on the chromatin. Nature Rev. Neurosci. 14, 97111 (2013).
  64. Hirano, Y. et al. Fasting launches CRTC to facilitate long-term memory formation in Drosophila. Science 339, 443446 (2013).
  65. Allis, C. D., Jenuwein, T., Reinberg, D. & Caparros, M. L. (eds) Epigenetics (Cold Spring Harbor Laboratory Press, 2007).
  66. Taylor, J. P. et al. Aberrant histone acetylation, altered transcription, and retinal degeneration in a Drosophila model of polyglutamine disease are rescued by CREB-binding protein. Genes Dev. 17, 14631468 (2003).
  67. Kim, T. K. et al. Widespread transcription at neuronal activity-regulated enhancers. Nature 465, 182187 (2010).
  68. Ringrose, L. & Paro, R. Polycomb/Trithorax response elements and epigenetic memory of cell identity. Development 134, 223232 (2007).
  69. Ferguson-Smith, A. C. Genomic imprinting: the emergence of an epigenetic paradigm. Nature Rev. Genet. 12, 565575 (2011).
  70. Cedar, H. & Bergman, Y. Linking DNA methylation and histone modification: patterns and paradigms. Nature Rev. Genet. 10, 295304 (2009).
  71. Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev. 16, 621 (2002).
  72. Lyko, F. & Maleszka, R. Insects as innovative models for functional studies of DNA methylation. Trends Genet. 27, 127131 (2011).
  73. Kronforst, M. R., Gilley, D. C., Strassmann, J. E. & Queller, D. C. DNA methylation is widespread across social Hymenoptera. Curr. Biol. 18, R287R288 (2008).
  74. Wang, Y. et al. Functional CpG methylation system in a social insect. Science 314, 645647 (2006).
    This is the first report to show that a social insect has a fully functional methylation system.
  75. Weiner, S. A. & Toth, A. L. Epigenetics in social insects: a new direction for understanding the evolution of castes. Genet. Res. Int. 2012, 609810 (2012).
  76. Glastad, K. M., Hunt, B. G. & Goodisman, M. A. Evidence of a conserved functional role for DNA methylation in termites. Insect Mol. Biol. 22, 143154 (2013).
  77. Wang, X. et al. Function and evolution of DNA methylation in Nasonia vitripennis. PLoS Genet. 9, e1003872 (2013).
  78. Kucharski, R., Maleszka, J., Foret, S. & Maleszka, R. Nutritional control of reproductive status in honeybees via DNA methylation. Science 319, 18271830 (2008).
    This paper presents the first functional evidence of the regulatory role of DNA methylation in regulating caste fate in eusocial insects.
  79. Gazin, C., Wajapeyee, N., Gobeil, S., Virbasius, C. M. & Green, M. R. An elaborate pathway required for Ras-mediated epigenetic silencing. Nature 449, 10731077 (2007).
  80. Popkie, A. P. et al. Phosphatidylinositol 3-kinase (PI3K) signaling via glycogen synthase kinase-3 (Gsk-3) regulates DNA methylation of imprinted loci. J. Biol. Chem. 285, 4133741347 (2010).
  81. Marks, H. et al. The transcriptional and epigenomic foundations of ground state pluripotency. Cell 149, 590604 (2012).
  82. Tee, W. W., Shen, S. S., Oksuz, O., Narendra, V. & Reinberg, D. Erk1/2 activity promotes chromatin features and RNAPII phosphorylation at developmental promoters in mouse ESCs. Cell 156, 678690 (2014).
  83. Spannhoff, A. et al. Histone deacetylase inhibitor activity in royal jelly might facilitate caste switching in bees. EMBO Rep. 12, 238243 (2011).
  84. Smith, C. R. et al. Patterns of DNA methylation in development, division of labor and hybridization in an ant with genetic caste determination. PLoS ONE 7, e42433 (2012).
  85. Foret, S. et al. DNA methylation dynamics, metabolic fluxes, gene splicing, and alternative phenotypes in honey bees. Proc. Natl Acad. Sci. USA 109, 49684973 (2012).
  86. Lockett, G. A., Wilkes, F. & Maleszka, R. Brain plasticity, memory and neurological disorders: an epigenetic perspective. Neuroreport 21, 909913 (2010).
  87. Li-Byarlay, H. et al. RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee. Proc. Natl Acad. Sci. USA 110, 1275012755 (2013).
  88. Rinn, J. L. & Chang, H. Y. Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 81, 145166 (2012).
  89. Greenberg, J. K. et al. Behavioral plasticity in honey bees is associated with differences in brain microRNA transcriptome. Genes Brain Behav. 11, 660670 (2012).
  90. Cabili, M. N. et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 25, 19151927 (2011).
  91. Humann, F. C., Tiberio, G. J. & Hartfelder, K. Sequence and expression characteristics of long noncoding RNAs in honey bee caste development — potential novel regulators for transgressive ovary size. PLoS ONE 8, e78915 (2013).
  92. Keller, L. Adaptation and the genetics of social behaviour. Phil. Trans. R. Soc. B 364, 32093216 (2009).
  93. Wang, J. et al. A Y-like social chromosome causes alternative colony organization in fire ants. Nature 493, 664668 (2013).
  94. Vecsey, C. G. et al. Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation. J. Neurosci. 27, 61286140 (2007).
  95. Beshers, S. N. & Fewell, J. H. Models of division of labor in social insects. Annu. Rev. Entomol. 46, 413440 (2001).
  96. Wheeler, W. M. & Weber, N. A. Mosaics and Other Anomalies Among Ants (Harvard Univ. Press, 1937).
  97. Kerr, W. E. Evolution of the mechanism of caste determination in the genus Melipona. Evolution 4, 713 (1950).
  98. Schwander, T., Lo, N., Beekman, M., Oldroyd, B. P. & Keller, L. Nature versus nurture in social insect caste differentiation. Trends Ecol. Evol. 25, 275282 (2010).
    This review summarizes the evidence of environmental and genetic effects on caste determination, and emphasizes the role of genetic variation on queen development in various eusocial insect species.
  99. Hughes, W. O. H., Sumner, S., Van Borm, S. & Boomsma, J. J. Worker caste polymorphism has a genetic basis in Acromyrmex leaf-cutting ants. Proc. Natl Acad. Sci. USA 100, 93949397 (2003).
  100. Schwander, T. & Keller, L. Genetic compatibility affects queen and worker caste determination. Science 322, 552 (2008).
  101. Smith, C. R., Toth, A. L., Suarez, A. V. & Robinson, G. E. Genetic and genomic analyses of the division of labour in insect societies. Nature Rev. Genet. 9, 735748 (2008).
    This is a thorough review on the genes and molecular pathways that are known to regulate caste determination and worker behavioural transitions in honeybees and other eusocial insects.
  102. Feldhaar, H., Foitzik, S. & Heinze, J. Review. Lifelong commitment to the wrong partner: hybridization in ants. Phil. Trans. R. Soc. B 363, 28912899 (2008).
  103. Frohschammer, S. & Heinze, J. A heritable component in sex ratio and caste determination in a Cardiocondyla ant. Front. Zool. 6, 27 (2009).
  104. Robinson, G. E. & Page, R. E. Genetic determination of guarding and undertaking in honeybee colonies. Nature 333, 356358 (1988).
  105. Stuart, R. J. & Page, R. E. Genetic component to division-of-labor among workers of a Leptothoracine ant. Naturwissenschaften 78, 375377 (1991).
  106. Rheindt, F. E., Strehl, C. P. & Gadau, J. A genetic component in the determination of worker polymorphism in the Florida harvester ant Pogonomyrmex badius. Insect Soc. 52, 163168 (2005).
  107. Anderson, K. E., Linksvayer, T. A. & Smith, C. R. The causes and consequences of genetic caste determination in ants (Hymenoptera: Formicidae). Myrmecol. News 11, 119132 (2008).
  108. Huang, M. H., Wheeler, D. E. & Fjerdingstad, E. J. Mating system evolution and worker caste diversity in Pheidole ants. Mol. Ecol. 22, 19982010 (2013).
  109. Hamilton, W. D. The genetical evolution of social behaviour. I. J. Theor. Biol. 7, 116 (1964).
  110. Hamilton, W. D. The genetical evolution of social behaviour. II. J. Theor. Biol. 7, 1752 (1964).
  111. Haig, D. The kinship theory of genomic imprinting. Annu. Rev. Ecol. Syst. 31, 932 (2000).
  112. Queller, D. C. Theory of genomic imprinting conflict in social insects. BMC Evol. Biol. 3, 15 (2003).
  113. Linksvayer, T. A. & Wade, M. J. The evolutionary origin and elaboration of sociality in the aculeate Hymenoptera: maternal effects, sib-social effects, and heterochrony. Q. Rev. Biol. 80, 317336 (2005).
  114. Kronauer, D. J. C. Genomic imprinting and kinship in the social Hymenoptera: what are the predictions? J. Theor. Biol. 254, 737740 (2008).
  115. Drewell, R. A., Lo, N., Oxley, P. R. & Oldroyd, B. P. Kin conflict in insect societies: a new epigenetic perspective. Trends Ecol. Evol. 27, 367373 (2012).
  116. Guzman-Novoa, E. et al. Paternal effects on the defensive behavior of honeybees. J. Hered. 96, 376380 (2005).
  117. Libbrecht, R. & Keller, L. Genetic compatibility affects division of labor in the Argentine ant Linepithema humile. Evolution 67, 517524 (2013).
  118. Khila, A. & Abouheif, E. Reproductive constraint is a developmental mechanism that maintains social harmony in advanced ant societies. Proc. Natl Acad. Sci. USA 105, 1788417889 (2008).
  119. Greer, E. L. et al. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature 479, 365371 (2011).
  120. Grossniklaus, U., Vielle-Calzada, J. P., Hoeppner, M. A. & Gagliano, W. B. Maternal control of embryogenesis by MEDEA, a Polycomb group gene in Arabidopsis. Science 280, 446450 (1998).
  121. Snell-Rood, E. C. An overview of the evolutionary causes and consequences of behavioural plasticity. Animal Behav. 85, 10041011 (2013).
  122. Snell-Rood, E. C., Troth, A. & Moczek, A. P. DNA methylation as a mechanism of nutritional plasticity: limited support from horned beetles. J. Exp. Zool. B Mol. Dev. Evol. 320, 2234 (2013).
  123. Nelson, C. M., Ihle, K. E., Fondrk, M. K., Page, R. E. & Amdam, G. V. The gene vitellogenin has multiple coordinating effects on social organization. PLoS Biol. 5, e62 (2007).
  124. Ratzka, C., Gross, R. & Feldhaar, H. Systemic gene knockdown in Camponotus floridanus workers by feeding of dsRNA. Insect Soc. 60, 475484 (2013).
  125. Hunt, J. H., Mutti, N. S., Havukainen, H., Henshaw, M. T. & Amdam, G. V. Development of an RNA interference tool, characterization of its target, and an ecological test of caste differentiation in the eusocial wasp polistes. PLoS ONE 6, e26641 (2011).
  126. Zhou, X. G., Wheeler, M. M., Oi, F. M. & Scharf, M. E. RNA interference in the termite Reticulitermes flavipes through ingestion of double-stranded RNA. Insect Biochem. Mol. Biol. 38, 805815 (2008).
  127. Filippakopoulos, P. et al. Selective inhibition of BET bromodomains. Nature 468, 10671073 (2010).
  128. Schulte, C., Theilenberg, E., Muller-Borg, M., Gempe, T. & Beye, M. Highly efficient integration and expression of piggyBac-derived cassettes in the honeybee (Apis mellifera). Proc. Natl Acad. Sci. USA 111, 90039008 (2014).
    This study is the first to show transgenics in a eusocial insect, which allows sophisticated genetic manipulations to be carried out in the honeybee.
  129. Patalano, S., Hore, T. A., Reik, W. & Sumner, S. Shifting behaviour: epigenetic reprogramming in eusocial insects. Curr. Opin. Cell Biol. 24, 367373 (2012).
  130. Rajakumar, R. et al. Ancestral developmental potential facilitates parallel evolution in ants. Science 335, 7982 (2012).
  131. Bonabeau, E., Theraulaz, G. & Deneubourg, J. L. Quantitative study of the fixed threshold model for the regulation of division of labour in insect societies. Proc. R. Soc. B 263, 15651569 (1996).
  132. Lattorff, H. M. & Moritz, R. F. Genetic underpinnings of division of labor in the honeybee (Apis mellifera). Trends Genet. 29, 641648 (2013).
  133. Bonasio, R. The role of chromatin and epigenetics in the polyphenisms of ant castes. Brief Funct. Genom. 13, 235245 (2014).
  134. Duncan, E. J., Gluckman, P. D. & Dearden, P. K. Epigenetics, plasticity, and evolution: how do we link epigenetic change to phenotype? J. Exp. Zool. Part B 322, 208220 (2014).
  135. Welch, M. & Lister, R. Epigenomics and the control of fate, form and function in social insects. Curr. Opin. Insect Sci. 1, 3138 (2014).
  136. Sasaki, T., Granovskiy, B., Mann, R. P., Sumpter, D. J. & Pratt, S. C. Ant colonies outperform individuals when a sensory discrimination task is difficult but not when it is easy. Proc. Natl Acad. Sci. USA 110, 1376913773 (2013).
  137. Linksvayer, T. A. in Encyclopedia of Animal Behavior (eds Breed, M. D. & Moore, J.) 358362 (Academic Press, 2010).
  138. LaPolla, J. S., Dlussky, G. M. & Perrichot, V. Ants and the fossil record. Annu. Rev. Entomol. 58, 609630 (2013).
  139. Ferreira, P. G. et al. Transcriptome analyses of primitively eusocial wasps reveal novel insights into the evolution of sociality and the origin of alternative phenotypes. Genome Biol. 14, R20 (2013).
  140. Johnson, B. R. et al. Phylogenomics resolves evolutionary relationships among ants, bees, and wasps. Curr. Biol. 23, 20582062 (2013).
  141. Schmidt, A. M., Linksvayer, T. A., Boomsma, J. J. & Pedersen, J. S. Queen-worker caste ratio depends on colony size in the pharaoh ant (Monomorium pharaonis). Insect Soc. 58, 139144 (2011).
  142. St Johnston, D. The art and design of genetic screens: Drosophila melanogaster. Nature Rev. Genet. 3, 176188 (2002).
  143. Kile, B. T. & Hilton, D. J. The art and design of genetic screens: mouse. Nature Rev. Genet. 6, 557567 (2005).
  144. Schmidt, A. M., Linksvayer, T. A., Boomsma, J. J. & Pedersen, J. S. No benefit in diversity? The effect of genetic variation on survival and disease resistance in a polygynous social insect. Ecol. Entomol. 36, 751759 (2011).
  145. Baer, B. & Schmid-Hempel, P. The artificial insemination of bumblebee queens. Insect Soc. 47, 183187 (2000).
  146. Kocher, S. D., Tarpy, D. R. & Grozinger, C. M. The effects of mating and instrumental insemination on queen honey bee flight behaviour and gene expression. Insect Mol. Biol. 19, 153162 (2010).
  147. den Boer, S. P. A., Boomsma, J. J. & Baer, B. A technique to artificially inseminate leafcutter ants. Insect Soc. 60, 111118 (2013).
  148. Hartenstein, V. The neuroendocrine system of invertebrates: a developmental and evolutionary perspective. J. Endocrinol. 190, 555570 (2006).
  149. Mutti, N. S. et al. IRS and TOR nutrient-signaling pathways act via juvenile hormone to influence honey bee caste fate. J. Exp. Biol. 214, 39773984 (2011).
  150. Tatar, M., Bartke, A. & Antebi, A. The endocrine regulation of aging by insulin-like signals. Science 299, 13461351 (2003).
  151. Penick, C. A., Prager, S. S. & Liebig, J. Juvenile hormone induces queen development in late-stage larvae of the ant Harpegnathos saltator. J. Insect Physiol. 58, 16431649 (2012).
  152. Jindra, M., Palli, S. R. & Riddiford, L. M. The juvenile hormone signaling pathway in insect development. Annu. Rev. Entomol. 58, 181204 (2013).
  153. Ament, S. A. et al. The transcription factor Ultraspiracle influences honey bee social behavior and behavior-related gene expression. PLoS Genet. 8, e1002596 (2012).
  154. Page, R. E. Jr, Scheiner, R., Erber, J. & Amdam, G. V. The development and evolution of division of labor and foraging specialization in a social insect (Apis mellifera L.). Curr. Top. Dev. Biol. 74, 253286 (2006).
  155. Page, R. E. Jr & Amdam, G. V. The making of a social insect: developmental architectures of social design. Bioessays 29, 334343 (2007).
  156. Libbrecht, R., Oxley, P. R., Kronauer, D. J. & Keller, L. Ant genomics sheds light on the molecular regulation of social organization. Genome Biol. 14, 212 (2013).
  157. Corona, M. et al. Vitellogenin underwent subfunctionalization to acquire caste and behavioral specific expression in the harvester ant Pogonomyrmex barbatus. PLoS Genet. 9, e1003730 (2013).

Download references

Author information

  1. These authors contributed equally to this work.

    • Hua Yan &
    • Daniel F. Simola

Affiliations

  1. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA.

    • Hua Yan &
    • Danny Reinberg
  2. Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

    • Daniel F. Simola,
    • Roberto Bonasio &
    • Shelley L. Berger
  3. Epigenetics Program, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

    • Daniel F. Simola,
    • Roberto Bonasio &
    • Shelley L. Berger
  4. School of Life Sciences, Arizona State University, Tempe, Arizona 85287–4501, USA.

    • Jürgen Liebig
  5. Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

    • Shelley L. Berger
  6. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

    • Shelley L. Berger
  7. Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016, USA.

    • Danny Reinberg

Competing interests statement

The authors declare no competing interests.

Corresponding authors

Correspondence to:

Author details

  • Hua Yan

    Hua Yan is a Ruth L. Kirschstein National Research Service Awards (NRSA) Postdoctoral Fellow in Danny Reinberg's laboratory at New York University School of Medicine, USA. He did his doctoral work with Cathie Pfleger and Zhen-Qiang Pan at the Icahn School of Medicine at Mount Sinai, New York. Currently, he is developing genetic tools and studies behavioural and aging plasticity of the ant species Harpegnathos saltator.

  • Daniel F. Simola

    Daniel F. Simola is a postdoctoral researcher in the laboratory of Shelley L. Berger at the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, USA. He led the first investigation of the role of histone modifications in regulating ant caste identity and the first comparative evolutionary analysis of the genomic basis of eusociality. His research interests pertain to the organization, regulation and evolution of behaviour in eusocial insects, as well as to computational methods for comparative and functional genomics. He is currently developing methods to deliver pharmaceutical compounds to ants and techniques to obtain multifactorial genome-wide information from single ant tissues.

  • Roberto Bonasio

    Roberto Bonasio is Assistant Professor of Cell and Developmental Biology, and a core member of the Epigenetics Program at the Perelman School of Medicine of the University of Pennsylvania, Philadelphia, USA. As a postdoctoral fellow at New York University, USA, he led the sequencing, annotation and analysis of the first genomes, transcriptomes and methylomes for the ant species Harpegnathos saltator and Camponotus floridanus. His laboratory investigates the molecular mechanisms of epigenetic memory using biochemistry and functional genomics in both conventional experimental systems (such as mammalian stem cells) and emerging model organisms (such as ants).

  • Jürgen Liebig

    Jürgen Liebig is an associate professor at Arizona State University, Tempe, USA. He received his Ph.D. (Dr. rer. nat.) at the University of Würzburg, Germany, in 1998. He was primarily interested in reproductive conflicts and the associated chemical signalling in ants. He played a central part in establishing the role of cuticular hydrocarbons as fertility signals in the regulation of reproduction in eusocial insects. Currently, he is extending his approach to understanding the organization of insect societies by the neurophysiology of olfactory communication, as well as the genetics and epigenetics of behavioural and developmental plasticity in ants and termites. Jürgen Liebig's homepage.

  • Shelley L. Berger

    Shelley L. Berger is the Daniel S. Och University Professor at the University of Pennsylvania, Philadelphia, USA; a faculty member in the Department of Cell and Developmental Biology, and the Department of Genetics in the Perelman School of Medicine of the University of Pennsylvania; a faculty member in the Biology Department in the School of Arts and Sciences at the University of Pennsylvania; and founder and Director of the Epigenetics Program in the Perelman School of Medicine. Her research focuses on the role of post-translational modifications of histones and factors in chromatin regulation and of the tumour suppressor p53. Her laboratory investigates the role of chromatin mechanisms in transcriptional regulation, as well as in the physiological processes of ageing, behaviour and gametogenesis, using a range of model systems such as yeast, ants, mice and mammalian cells. Shelley L. Berger's homepage.

  • Danny Reinberg

    Danny Reinberg is an Howard Hughes Medical Institute (HHMI) investigator and Professor in the Department of Biochemistry and Molecular Pharmacology at New York University Langone Medical School, USA. Previously, he was Distinguished Professor at the University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School. Danny Reinberg's homepage.

Additional data