DNA methylation is widespread and associated with differential gene expression in castes of the honeybee, <i>Apis mellifera</i>

<jats:p> The recent, unexpected discovery of a functional DNA methylation system in the genome of the social bee <jats:italic>Apis mellifera</jats:italic> underscores the potential importance of DNA methylation in invertebrates. The extent of genomic DNA methylation and its role in <jats:italic>A. mellifera</jats:italic> remain unknown, however. Here we show that genes in <jats:italic>A. mellifera</jats:italic> can be divided into 2 distinct classes, one with low-CpG dinucleotide content and the other with high-CpG dinucleotide content. This dichotomy is explained by the gradual depletion of CpG dinucleotides, a well-known consequence of DNA methylation. The loss of CpG dinucleotides associated with DNA methylation also may explain the unusual mutational patterns seen in <jats:italic>A. mellifera</jats:italic> that lead to AT-rich regions of the genome. A detailed investigation of this dichotomy implicates DNA methylation in <jats:italic>A. mellifera</jats:italic> development. High-CpG genes, which are predicted to be hypomethylated in germlines, are enriched with functions associated with developmental processes, whereas low-CpG genes, predicted to be hypermethylated in germlines, are enriched with functions associated with basic biological processes. Furthermore, genes more highly expressed in one caste than another are overrepresented among high-CpG genes. Our results highlight the potential significance of epigenetic modifications, such as DNA methylation, in developmental processes in social insects. In particular, the pervasiveness of DNA methylation in the genome of <jats:italic>A. mellifera</jats:italic> provides fertile ground for future studies of phenotypic plasticity and genomic imprinting. </jats:p>