The Honey Bee Gene Is a Taxonomically Restricted Antiviral Immune Gene.

Insects have evolved a wide range of strategies to combat invading pathogens, including viruses. Genes that encode proteins involved in immune responses often evolve under positive selection due to their co-evolution with pathogens. Insect antiviral defense includes the RNA interference (RNAi) mechanism, which is triggered by recognition of non-self, virally produced, double-stranded RNAs. Indeed, insect RNAi genes (e.g., and ) are under high selective pressure. Honey bees () are eusocial insects that respond to viral infections both sequence specific RNAi and a non-sequence specific dsRNA triggered pathway, which is less well-characterized. A transcriptome-level study of virus-infected and/or dsRNA-treated honey bees revealed increased expression of a novel antiviral gene, GenBank: MF116383, and experiments confirmed its antiviral function. Due to annotation and sequence similarity, MF116383 was originally annotated as a probable . In this study, we confirmed that MF116383 limits virus infection, and carried out further bioinformatic and phylogenetic analyses to better characterize this important gene-which we renamed (). Phylogenetic analysis revealed that is taxonomically restricted to Hymenoptera and (the German cockroach) and that the majority of amino acids are evolving under neutral selection. This is in-line with the results from structural prediction tools that indicate Bap1 is a highly disordered protein, which likely has relaxed structural constraints. Assessment of honey bee gene expression using a weighted gene correlation network analysis revealed that expression was highly correlated with several immune genes-most notably . The coexpression of and was confirmed in an independent dataset that accounted for the effect of virus abundance. Together, these data demonstrate that is a taxonomically restricted, rapidly evolving antiviral immune gene. Future work will determine the role of in limiting replication of other viruses and examine the signal cascade responsible for regulating the expression of and other honey bee antiviral defense genes, including coexpressed , and determine whether the virus limiting function of acts in parallel or in tandem with RNAi.