Genomic analysis of the interaction between pesticide exposure and nutrition in honey bees (Apis mellifera) Daniel R. Schmehl a,⇑ , Peter E.A. Teal b , James L. Frazier a , Christina M. Grozinger a,1 a Department of Entomology, Center for Pollinator Research, The Pennsylvania State University, University Park, PA, USA b United States Department of Agriculture, Agricultural Research Service, Gainesville, FL, USA article info Article history: Received 5 July 2014 Received in revised form 19 September 2014 Accepted 6 October 2014 Available online xxxx Keywords: Honey bee Pesticide Nutrition Stress Transcription Genomics abstract Populations of pollinators are in decline worldwide. These declines are best documented in honey bees and are due to a combination of stressors. In particular, pesticides have been linked to decreased longev- ity and performance in honey bees; however, the molecular and physiological pathways mediating sen- sitivity and resistance to pesticides are not well characterized. We explored the impact of coumaphos and fluvalinate, the two most abundant and frequently detected pesticides in the hive, on genome-wide gene expression patterns of honey bee workers. We found signif- icant changes in 1118 transcripts, including genes involved in detoxification, behavioral maturation, immunity, and nutrition. Since behavioral maturation is regulated by juvenile hormone III (JH), we examined effects of these miticides on hormone titers; while JH titers were unaffected, titers of methyl farnesoate (MF), the precursor to JH, were decreased. We further explored the association between nutri- tion- and pesticide-regulated gene expression patterns and demonstrated that bees fed a pollen-based diet exhibit reduced sensitivity to a third pesticide, chlorpyrifos. Finally, we demonstrated that expres- sion levels of several of the putative pesticide detoxification genes identified in our study and previous studies are also upregulated in response to pollen feeding, suggesting that these pesticides and compo- nents in pollen modulate similar molecular response pathways. Our results demonstrate that pesticide exposure can substantially impact expression of genes involved in several core physiological pathways in honey bee workers. Additionally, there is substantial overlap in responses to pesticides and pollen-containing diets at the transcriptional level, and subsequent analyses demonstrated that pollen-based diets reduce workers’ pesticide sensitivity. Thus, providing honey bees and other pollinators with high quality nutrition may improve resistance to pesticides. Ó 2014 Published by Elsevier Ltd. 1. Introduction Pollinators are critical to production of approximately 70% of our agricultural crops, particularly nutrient-rich fruits, vegetables and nuts (Eilers et al., 2011; Klein et al., 2007). However, popula- tions of honey bees and other pollinators are in decline globally (González-Varo et al., 2013; Potts et al., 2010), with US beekeepers losing approximately 30% of their colonies each winter (vanEngelsdorp et al., 2012). These declines have been attributed to multiple factors, including pathogens, parasites, habitat loss and fragmentation, and intensive mono-cropping systems which lead to reduced floral resources and nutrition (Potts et al., 2010). In addition to these factors, there have been mounting concerns about the effects of pesticides (Council, 2007; Godfray et al., 2014; Sanchez-Bayo and Goka, 2014). Indeed, residues from over 120 different pesticides have been found in honey bee colonies in the US, with an average of six pesticides found in the stored pol- len of these colonies (Mullin et al., 2010). Two pesticides in partic- ular, fluvalinate and coumaphos, are the most prevalent (found in 98% of the 749 colonies surveyed) and are found at the highest http://dx.doi.org/10.1016/j.jinsphys.2014.10.002 0022-1910/Ó 2014 Published by Elsevier Ltd. Abbreviations: JH, juvenile hormone III; MF, methyl farnesoate; P450, cyto- chrome P450 monooxygenase; FDR, false discovery rate; CCE, carboxyl/cholines- terase; GST, glutathione-S-transferase; GO, gene ontogeny; qRT-PCR, quantitative real-time polymerase chain reaction; SDI, single drone inseminated; Qeq, queen equivalent; LC/MS–MS, liquid chromatography–mass spectrometry–mass spec- trometry; GC/MS, gas chromatography–mass spectrometry; GSTD1, glutathione S- transferase D1; SODH2, superoxide dismutase. ⇑ Corresponding author at: Entomology and Nematology Department, University of Florida, 970 Natural Area Drive, Steinmetz Hall, Gainesville, FL 32611, USA. Tel.: +1 (352) 273 3935. E-mail addresses: danielrschmehl@ufl.com (D.R. Schmehl), peter.teal@ars.usda. gov (P.E.A. Teal), jff2@psu.edu (J.L. Frazier), cmgrozinger@psu.edu (C.M. Grozinger). 1 Co-corresponding author. Journal of Insect Physiology xxx (2014) xxx–xxx Contents lists available at ScienceDirect Journal of Insect Physiology journal homepage: www.elsevier.com/locate/jinsphys Please cite this article in press as: Schmehl, D.R., et al. Genomic analysis of the interaction between pesticide exposure and nutrition in honey bees (Apis mellifera). Journal of Insect Physiology (2014), http://dx.doi.org/10.1016/j.jinsphys.2014.10.002