Eusocial insects as emerging models for behavioural epigenetics

Journal name:
Nature Reviews Genetics
Year published:
Published online
Corrected online


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


  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".


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Author information

  1. These authors contributed equally to this work.

    • Hua Yan &
    • Daniel F. Simola


  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

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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.

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