1. SIBO: A Social Insect Behavior Ontology for Ants and Bees Christopher D. Smith Ph.D. Assistant Professor Bioinformatics San Francisco State University San Francisco, CA 94132 smithcd@sfsu.edu Drosophila Heterochromatin Genome Project Lawrence Berkeley National Lab Berkeley, CA 94720 www.dhgp.org cdsmith@fruitfly.org

2. Drosophila melanogaster 100 years of experimental data ‘Complete’ sequenced genome Many well-characterized behavior & other phenotypes Microarray & other large scale datasets Adams & Venter et. al. Science. 2000 Mar 24;287(5461):2185-95.Science.

3. Genes Often Very Conserved in Metazoans Eyeless is a classic example –No eyes in flies, mice –Human Blindness (Aniridia) Numerous Other examples –Alcoholism cheapdate = cAMP signaling LUSH = odorant receptor –Learning & Memory dunce = cAMP metabolism –Limb Development (Homeotic)

4. Cooperativity: D. melanogaster dunce gene involved in learning & group behavior dunce = cAMP phosphodiesterase ‘Search Aggregation’ in Drosophila: group advantage in finding good Tinette & Robichon. Genes Brain Behav. 2004 Feb;3(1):39-50. dunce overexpressed on worker bees relative to queen in bees Judice & Pereira. Insect Molecular Biology (2006) 15 (1), 33-44. dunce ortholog & dunce-like genes related to schizophrenia in humans Millar & Morteous. Science Vol.310. no. 5751, pp. 1187.

5. Numerous Insect Genomes Available Million Years

6. Eusocial Insects Are Overdue for Genomics Extensive Natural History & Literature Behavior Assays Already Developed Extensive Epigenetic Caste Regulation –Lifespan –Morphology –Complex Social Behavior Leverage Drosophila and use genetic, genomic, phenotype data Social Insect Similarities to Humans –Dominant global species –Individualism –Slavery, Policing reviewed in “The Ants” E. O Wilson –Agriculture Mueller & Schultz. Science, v281:2034 –Teaching Franks & Richardson. Nature. v439:153 >11,500 Ant species >25,000 Bee species >2800 Termite Species Grimaldie & Engel Evolution of the Insects Cambridge University Press

7. Eusocial Insects Differeniate into Castes with Distinct Behaviors & Shapes Image Credit : Amy Beaton, Rubin Lab http://www.bdgp.org/cgi-bin/ex/insitu.pl Eusocial Hallmarks –Division of labor- Workers, Soldier, Queens, etc… –Sterile Castes (not req’d)- Single & Multiple Queens possible –Multiple generations lives in nest - Older generations care for younger Social behavior NOT genetically defined –Eusocial behavior has arisen many times in different species –Genetic predisposition, but no ‘hard-corded’ castes –Castes are temporally regulated in some species Behavior is epigenetically regulated –Genetically identical individuals express different phenotypes

8. Caste Programming Depend on Hormones & Environment Cues Abouheif & Wray Evolution of the Gene Network Underlying Wing Polyphenism in Ants Science 12 July 2002: Vol. 297. no. 5579, pp. 249 - 252 JH = Juvenile Hormone

9. Covergent Behaviors in Ants & Bees

10. Worker & Queen Bees Express Unique Gene Subsets Wheeler et. al. Expression profiles during honeybee caste determination GenomeBiology2000, 2(1):research0001.1-0001.6 Genetically identical animals exhibit widely varied gene expression profiles Numerous caste specific genes have been identified in bees, ants & termites With completion of ‘beenome’ many more behavioral microarray expts. planned

11. Identification of Putative Orthologs  TBLASTN approach using the Comparative Genomics Library (CGL)  Best ‘multiple-hit’ used to determine orthologous exons  Orthologous introns inferred when both flanking exons are found CG40919

12. Behaviors can be linked to SNPs Africanized bees –Pursue Enemy 10-30x further –More reactive to color, movement –4-10x stinging –Disengage less –Alert quickly –Larger defense perimeter Using comparative annotation we can link ‘Africanized’ SNPs to gene and regulatory annotations –e.g. Dopamine receptor mutations DRD4 –e.g. Serotonin promoter polymorphism hSlc6a4,dSerT Disengagement Perception Orientation 1 o Discrimination or Identification Alert Recruitment Approach 2 o Discrimination or Identification Threat ATTACK! Adapted from Breed & Hunt 2004. Annu. Rev. Entolom. 49:271-98

13. Seeding the Ontology Currently only 100 terms Estimated 3500 behaviors in ants and bees Derived from Drosophila GO behavior terms and bee/ant literature

14. Link Behaviors to ‘Language’ Genes Ants have more chemical producing glands than any known organism –Queens can chemically inhibit fertility through colony –Queens can call ‘group alarm’ for attack & defense –Workers can communicate novel information to others back and forth (i.e. teaching) Link Behaviors to Chemicals –e.g. ‘Mortician Ants’ respond to oleate from decomposition Reviewed in Holldobler & Wilson, The Ants, 1990

15. Eusocial Insects Use a Complex Chemical Language that is Genetically Defined Language is an important aspect of social evolution across taxa –High-density –Peer Conflict Resolution –Division of labor –Group Defense Ants Can ‘Read’ Hundreds of Chemicals –Few receptors known Biogenic Amines –e.g. octapamine involved in honeybee aggression –Few genes identified Reviewed in Holldobler & Wilson, The Ants, 1990

16. Semiochemical & Anatomy Ontology derives_from relationships need to be defined

17. Linking Behavior, Anatomy, & Semiochemicals

18. Present & Future work Collection of terms & definition from honeybee and ant literature & community Prioritization of behaviors associated to genes discovered in behavioral microarray experiments Curation of ‘derives_from’ relationships for semiochemicals and anatomy Curation of ‘precedes’ and ‘follows’ relationships for behavior actions (e.g. mating) Adaptation of Drosophila anatomy onotology for honeybees and ants Determination of cross-products with other ontologies such as CHEBI and GO

19. Ackowledgements Drosophila Heterochromatin Genome Project (DHGP) –Chris Mungall - Databases, Ontologies –Nicole Washington - PATO –Suzanna Lewis- Group Leader –John Richter - OBO-Edit Collaborators –Neil Tsutsui - UC Irvine –Chris Elsik - BeeBase

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