The highly organized societies of the Western honey bee Apis mellifera feature a highly reproductive queen at the center of attention and a large cohort of daughters that suppress their own reproduction to help rear more sisters, some of whom become queens themselves. This reproductive altruism is peculiar because in theory it evolves via indirect selection on genes for altruism that are expressed in the sterile workers but not in the reproductive queens. In this study we attempt to situate lists of genes previously implicated in queenright worker sterility into a broader regulatory framework. To do so we use a model bee brain transcriptional regulatory network as a template to infer how sets of genes responsive to ovary-suppressing queen pheromone are functionally interconnected over the model's topology. We predict that genes jointly involved in the regulation of worker sterility should be tightly networked, relative to genes whose functions are unrelated to each other. We find that sets of mapped genes – ranging in size from 17 to 250 – are well dispersed across the network's substructural scaffolds, suggesting that ovary de-activation involves genes that reside within more than one transcriptional regulatory module. For some sets, however, this dispersion is biased into certain areas of the network's substructure. Our analysis identifies the regions enriched for sterility genes and likewise identifies local hub genes that are presumably critical to subnetwork function. Our work offers a glimpse into the gene regulatory context of honey bee worker sterility and uses this context to identify new candidate gene targets for functional analysis. Finally, to the extent that any sterility-related modules identified here have evolved via selection for worker altruism, we can assume that this selection was indirect and of the type specifically invoked by inclusive fitness theory.

西方蜜蜂Apis mellifera高度组织化的社会以高度繁殖的女王为关注的焦点，还有一大群抑制自己繁殖的女儿，以帮助养育更多的姐妹，其中一些自己成为了女王。这种生殖利他主义是奇特的，因为理论上它是通过间接选择利他主义基因而进化的，这些基因在不育的工蚁中表达，但在繁殖的蜂王中不表达。在这项研究中，我们试图将先前与女权工人不育有关的基因列表置于更广泛的监管框架中。为此，我们使用模型蜜蜂大脑转录调控网络作为模板来推断对卵巢抑制女王信息素有反应的基因组如何通过模型的拓扑结构在功能上相互关联。我们预测共同参与调节工人不育的基因应该是紧密相连的，相对于功能彼此无关的基因。我们发现一组映射基因——大小从 17 到 250 不等——很好地分散在网络的亚结构支架中，这表明卵巢失活涉及位于多个转录调控模块中的基因。然而，对于某些集合，这种分散偏向于网络子结构的某些区域。我们的分析确定了富含不育基因的区域，同样也确定了可能对子网功能至关重要的局部中心基因。我们的工作提供了对蜜蜂工人不育的基因调控背景的一瞥，并使用这种背景来确定用于功能分析的新候选基因目标。最后，