Genetics of tolerance in honeybees to the neonicotinoid clothianidin

The effects of neonicotinoid insecticides (NNIs) on honeybee health are intensely debated, with numerous studies showing negative effects of exposure, while others report no such effects. We carried out experiments to study the genetic and molecular basis of NNI tolerance in honeybees, which may underlie the discrepancies observed in the literature. We discovered that worker survival post-exposure to an acute oral dose of clothianidin is heritable (H² = 37.8%). Tolerance to clothianidin was not associated with differences in the expression of detoxification enzymes in our experiments. Instead, mutations in the primary neonicotinoid detoxification genes CYP9Q1 and CYP9Q3 were strongly associated with worker survival post-clothianidin exposure. In some instances, the strong association between CYP9Q haplotypes and worker survival was associated with the protein's predicted binding affinity for clothianidin. Our findings have implications regarding future toxicological studies utilizing honeybees as a model pollinator.