Individual differences in honey bee behavior enabled by plasticity in brain gene regulatory networks

Understanding the regulatory architecture of phenotypic variation is a fundamental goal in biology, but connections between gene regulatory network (GRN) activity and individual differences in behavior are poorly understood. We characterized the molecular basis of behavioral plasticity in queenless honey bee (Apis mellifera) colonies, where individuals engage in both reproductive and non-reproductive behaviors. Using high-throughput behavioral tracking, we discovered these colonies contain a continuum of phenotypes, with some individuals specialized for either egg-laying or foraging and ‘generalists’ that perform both. Brain gene expression and chromatin accessibility profiles were correlated with behavioral variation, with generalists intermediate in behavior and molecular profiles. Models of brain GRNs constructed for individuals revealed that transcription factor (TF) activity was highly predictive of behavior, and behavior-associated regulatory regions had more TF motifs. These results provide new insights into the important role played by brain GRN plasticity in the regulation of behavior, with implications for social evolution.

[1]  Martin Middendorf,et al.  Automated monitoring of animal behaviour with barcodes and convolutional neural networks , 2020, bioRxiv.

[2]  Beryl M. Jones,et al.  Behavior-related gene regulatory networks: A new level of organization in the brain , 2020, Proceedings of the National Academy of Sciences.

[3]  Beryl M. Jones,et al.  Developmental plasticity shapes social traits and selection in a facultatively eusocial bee , 2020, Proceedings of the National Academy of Sciences.

[4]  C. Finet,et al.  Temporal flexibility of gene regulatory network underlies a novel wing pattern in flies , 2020, Proceedings of the National Academy of Sciences.

[5]  Gene E. Robinson,et al.  Honey bee virus causes context-dependent changes in host social behavior , 2020, Proceedings of the National Academy of Sciences.

[6]  A. Bell,et al.  Neurogenomic insights into paternal care and its relation to territorial aggression , 2019, Nature Communications.

[7]  G. Robinson,et al.  Division of labor in honey bees is associated with transcriptional regulatory plasticity in the brain , 2019, Journal of Experimental Biology.

[8]  Giulia Antonazzo,et al.  FlyBase 2.0: the next generation , 2018, Nucleic Acids Res..

[9]  G. Robinson,et al.  Quantifying the effects of pollen nutrition on honey bee queen egg laying with a new laboratory system , 2018, PloS one.

[10]  I. Amit,et al.  Salient experiences are represented by unique transcriptional signatures in the mouse brain , 2018, eLife.

[11]  Martin Middendorf,et al.  Automated monitoring of behavior reveals bursty interaction patterns and rapid spreading dynamics in honeybee social networks , 2018, Proceedings of the National Academy of Sciences.

[12]  G. Robinson,et al.  Behavioral, transcriptomic and epigenetic responses to social challenge in honey bees , 2017, Genes, brain, and behavior.

[13]  L. Stubbs,et al.  Temporal dynamics of neurogenomic plasticity in response to social interactions in male threespined sticklebacks , 2017, PLoS genetics.

[14]  Joseph M. Troy,et al.  Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice. , 2017, Genome research.

[15]  Seán G. Brady,et al.  Phylogenomic Insights into the Evolution of Stinging Wasps and the Origins of Ants and Bees , 2017, Current Biology.

[16]  Beryl M. Jones,et al.  Caste-biased gene expression in a facultatively eusocial bee suggests a role for genetic accommodation in the evolution of eusociality , 2017, Proceedings of the Royal Society B: Biological Sciences.

[17]  G. Robinson,et al.  Endocrine Influences on Insect Societies , 2017 .

[18]  Yuan Yu,et al.  TensorFlow: A system for large-scale machine learning , 2016, OSDI.

[19]  J. Witte.  The Ants , 2016 .

[20]  Anandasankar Ray,et al.  Epigenetic (re)programming of caste-specific behavior in the ant Camponotus floridanus , 2016, Science.

[21]  Fernando Wario,et al.  Automatic methods for long-term tracking and the detection and decoding of communication dances in honeybees , 2015, Front. Ecol. Evol..

[22]  Ofer Feinerman,et al.  Ant trophallactic networks: simultaneous measurement of interaction patterns and food dissemination , 2015, Scientific Reports.

[23]  Matthew E. Hudson,et al.  Genomic signatures of evolutionary transitions from solitary to group living , 2015, Science.

[24]  Andrew M. Mountcastle,et al.  BEEtag: A Low-Cost, Image-Based Tracking System for the Study of Animal Behavior and Locomotion , 2015, bioRxiv.

[25]  Howard Y. Chang,et al.  ATAC‐seq: A Method for Assaying Chromatin Accessibility Genome‐Wide , 2015, Current protocols in molecular biology.

[26]  Saurabh Sinha,et al.  Neuromolecular responses to social challenge: Common mechanisms across mouse, stickleback fish, and honey bee , 2014, Proceedings of the National Academy of Sciences.

[27]  Andreas R. Pfenning,et al.  Core and region-enriched networks of behaviorally regulated genes and the singing genome , 2014, Science.

[28]  Daniel L. Mace,et al.  Regulatory analysis of the C. elegans genome with spatiotemporal resolution , 2014, Nature.

[29]  S. Chandrasekaran,et al.  Predicting Phenotype from Genotype Through Reconstruction and Integrative Modeling of Metabolic and Regulatory Networks , 2014 .

[30]  C. Kent,et al.  Population genomics of the honey bee reveals strong signatures of positive selection on worker traits , 2014, Proceedings of the National Academy of Sciences.

[31]  Howard Y. Chang,et al.  Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position , 2013, Nature Methods.

[32]  G. Robinson,et al.  Brain gene expression changes elicited by peripheral vitellogenin knockdown in the honey bee , 2013, Insect molecular biology.

[33]  Nicholas L. Naeger,et al.  Altruistic Behavior by Egg-Laying Worker Honeybees , 2013, Current Biology.

[34]  A. Crespi,et al.  Tracking Individuals Shows Spatial Fidelity Is a Key Regulator of Ant Social Organization , 2013, Science.

[35]  G. Amdam,et al.  Genetics of reproduction and regulation of honeybee (Apis mellifera L.) social behavior. , 2012, Annual review of genetics.

[36]  Gene E Robinson,et al.  Understanding the relationship between brain gene expression and social behavior: lessons from the honey bee. , 2012, Annual review of genetics.

[37]  M. Brenner,et al.  Closely related bird species demonstrate flexibility between beak morphology and underlying developmental programs , 2012, Proceedings of the National Academy of Sciences.

[38]  Johannes E. Schindelin,et al.  Fiji: an open-source platform for biological-image analysis , 2012, Nature Methods.

[39]  T. Bailey,et al.  Inferring direct DNA binding from ChIP-seq , 2012, Nucleic acids research.

[40]  Zhengzheng S Liang,et al.  The Transcription Factor Ultraspiracle Influences Honey Bee Social Behavior and Behavior-Related Gene Expression , 2012, PLoS genetics.

[41]  James A. Eddy,et al.  Behavior-specific changes in transcriptional modules lead to distinct and predictable neurogenomic states , 2011, Proceedings of the National Academy of Sciences.

[42]  H. Nijhout,et al.  optix Drives the Repeated Convergent Evolution of Butterfly Wing Pattern Mimicry , 2011, Science.

[43]  Brielle J. Fischman,et al.  Genes involved in convergent evolution of eusociality in bees , 2011, Proceedings of the National Academy of Sciences.

[44]  H. Gençer,et al.  Are sperm traits of drones (Apis mellifera L.) from laying worker colonies noteworthy? , 2011 .

[45]  Saurabh Sinha,et al.  FlyFactorSurvey: a database of Drosophila transcription factor binding specificities determined using the bacterial one-hybrid system , 2010, Nucleic Acids Res..

[46]  G. Amdam,et al.  Support for the reproductive ground plan hypothesis of social evolution and major QTL for ovary traits of Africanized worker honey bees (Apis mellifera L.) , 2011, BMC Evolutionary Biology.

[47]  S. Johnson,et al.  The missing stink: sulphur compounds can mediate a shift between fly and wasp pollination systems , 2010, Proceedings of the Royal Society B: Biological Sciences.

[48]  Matthew E. Hudson,et al.  associated with behaviour across social insect lineages Brain transcriptomic analysis in paper wasps identifies genes , 2010 .

[49]  G. Robinson,et al.  Learning and task interference by corpse-removal specialists in honey bee colonies , 2010 .

[50]  S. Carroll,et al.  Generation of a novel wing colour pattern by the Wingless morphogen , 2010, Nature.

[51]  Jeremy Schmutz,et al.  Adaptive Evolution of Pelvic Reduction in Sticklebacks by Recurrent Deletion of a Pitx1 Enhancer , 2010, Science.

[52]  G. Robinson,et al.  Regulation of brain gene expression in honey bees by brood pheromone , 2009, Genes, brain, and behavior.

[53]  Israel Steinfeld,et al.  BMC Bioinformatics BioMed Central , 2008 .

[54]  A. Dornhaus.  Specialization Does Not Predict Individual Efficiency in an Ant , 2008, PLoS biology.

[55]  G. Amdam,et al.  Sensory Response System of Social Behavior Tied to Female Reproductive Traits , 2008, PloS one.

[56]  Raphaël Jeanson,et al.  Division of labour and socially induced changes in response thresholds in associations of solitary halictine bees , 2008, Animal Behaviour.

[57]  R. Gadagkar.  The evolution of caste polymorphism in social insects:0 Genetic release followed by diversifying evolution , 1997, Journal of Genetics.

[58]  Tom Wenseleers,et al.  Altruism in insect societies and beyond: voluntary or enforced? , 2008, Trends in ecology & evolution.

[59]  Molly E Cummings,et al.  Sexual and social stimuli elicit rapid and contrasting genomic responses , 2007, Proceedings of the Royal Society B: Biological Sciences.

[60]  M. Winston,et al.  Genome‐wide analysis reveals differences in brain gene expression patterns associated with caste and reproductive status in honey bees (Apis mellifera) , 2007, Molecular ecology.

[61]  Cheng Li,et al.  Adjusting batch effects in microarray expression data using empirical Bayes methods. , 2007, Biostatistics.

[62]  T. Wenseleers,et al.  Enforced altruism in insect societies , 2006, Nature.

[63]  Chengxiang Zhai,et al.  Genome scan for cis-regulatory DNA motifs associated with social behavior in honey bees , 2006, Proceedings of the National Academy of Sciences.

[64]  S. Carroll,et al.  Repeated morphological evolution through cis-regulatory changes in a pleiotropic gene , 2006, Nature.

[65]  S. Sakagami,et al.  Occurrence of an aggressive behaviour in queenless hives, with considerations on the social organization of honeybee , 1954, Insectes Sociaux.

[66]  K. Foster,et al.  Conflict resolution in insect societies. , 2006, Annual review of entomology.

[67]  M. Lindauer.  The social behavior of the bees: a comparative study , 1976, Insectes Sociaux.

[68]  L. Lester,et al.  Juvenile hormone promotes dominance behavior and ovarian development in social wasps (Polistes annularis) , 1975, Experientia.

[69]  G. Robinson,et al.  Reproductive competition in queenless honey bee colonies (Apis mellifera L.) , 1994, Behavioral Ecology and Sociobiology.

[70]  F. Ratnieks,et al.  Egg-laying, egg-removal, and ovary development by workers in queenright honey bee colonies , 1993, Behavioral Ecology and Sociobiology.

[71]  G. Robinson,et al.  Intracolonial behavioral variation in worker oviposition, oophagy, and larval care in queenless honey bee colonies , 1990, Behavioral Ecology and Sociobiology.

[72]  R. E. Page,et al.  Reproduction by worker honey bees (Apis mellifera L.) , 1988, Behavioral Ecology and Sociobiology.

[73]  Edward O. Wilson,et al.  Caste and division of labor in leaf-cutter ants (Hymenoptera: Formicidae: Atta) , 1983, Behavioral Ecology and Sociobiology.

[74]  Edward O. Wilson,et al.  Caste and division of labor in leaf-cutter ants (Hymenoptera: Formicidae: Atta) , 1980, Behavioral Ecology and Sociobiology.

[75]  G. Robinson,et al.  Gene Expression Profiles in the Brain Predict Behavior in Individual Honey Bees , 2003, Science.

[76]  Saurabh Sinha,et al.  A probabilistic method to detect regulatory modules , 2003, ISMB.

[77]  J. Schmidt,et al.  Colony development, larval development and worker reproduction in Bombus impatiens Cresson , 2002, Insectes Sociaux.

[78]  F. Ratnieks,et al.  The timing of worker reproduction and breakdown of policing behaviour in queenless honey bee (Apis mellifera L.) societies , 2001, Insectes Sociaux.

[79]  G. Robinson,et al.  Biogenic amines and division of labor in honey bee colonies: behaviorally related changes in the antennal lobes and age-related changes in the mushroom bodies , 1999, Journal of Comparative Physiology A.

[80]  G. Benson,et al.  Tandem repeats finder: a program to analyze DNA sequences. , 1999, Nucleic acids research.

[81]  S. O’Donnell.  Reproductive caste determination in eusocial wasps (Hymenoptera: Vespidae). , 1998, Annual review of entomology.

[82]  P. Visscher,et al.  Reproductive conflict in honey bees: a stalemate of worker egg-laying and policing , 1996, Behavioral Ecology and Sociobiology.

[83]  M. West-Eberhard,et al.  Natural history and evolution of paper-wasps , 1996 .

[84]  T. Seeley.  The Wisdom of the Hive: The Social Physiology of Honey Bee Colonies , 1995 .

[85]  Jean-Marie Cornuet,et al.  Precise assessment of the number of patrilines and of genetic relatedness in honeybee colonies , 1994, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[86]  J. Lobo,et al.  Estimation of the number of matings in Apis mellifera: extensions of the model and comparison of different estimates , 1993 .

[87]  G. Robinson,et al.  Reproduction in worker honey bees is associated with low juvenile hormone titers and rates of biosynthesis. , 1992, General and comparative endocrinology.

[88]  D. Vicario,et al.  Song presentation induces gene expression in the songbird forebrain. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[89]  G. Robinson.  Regulation of division of labor in insect societies. , 1992, Annual review of entomology.

[90]  R. E. Page,et al.  The Genetics of Division of Labour in Honey Bee Colonies , 1991 .

[91]  H. Velthuis,et al.  Ovarian development and egg laying in workers of Bombus terrestris , 1989 .

[92]  Diana E. Wheeler,et al.  Developmental and Physiological Determinants of Caste in Social Hymenoptera: Evolutionary Implications , 1986, The American Naturalist.

[93]  E. Wilson,et al.  Caste and ecology in the social insects. , 1979, Monographs in population biology.

[94]  J. Adams,et al.  Estimation of the number of sex alleles and queen matings from diploid male frequencies in a population of Apis mellifera. , 1977, Genetics.

[95]  C. Brooke Worth,et al.  The Insect Societies , 1973 .

[96]  H. Velthuis,et al.  OVARIAN DEVELOPMENT IN APIS MELLIFERA WORKER BEES , 1970 .

[97]  A. Woodrow.  The Hive and the Honey Bee , 1964 .

[98]  J. Free.  The behaviour of egg-laying workers of bumblebee colonies , 1955 .

[99]  Gertrud Hess.  Ueber den Einfluss der Weisellosigkeit und des Fruchtbarkeitsvitamins E auf die Ovarien der Bienenarbeiterin , 1942 .