ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR285/SRR285020/SRR285020_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR285/SRR285020/SRR285020_1.fastq.gzprimary200OKGenomicsEpigenetics, Diabetes, Blizard Institutehttps://www.ebi.ac.uk/ena/browser/view/PRJNA140771Apis melliferaHere, we demonstrate that Nematostella vectensis, Ciona intestinalis, Apis mellifera, and B. mori, show two distinct populations of genes differentiated by gene-body CpG density. Genome-scale DNA methylation profiles for A. mellifera spermatozoa reveal CpG-poor genes are methylated in the germ line, as predicted by the depletion of CpGs. We find an evolutionarily conserved distinction between CpG-poor and -rich genes: the former are associated with basic biological processes, the latter with more specialized functions. This distinction is strikingly similar to that recently observed between euchromatin-associated genes in Drosophila that contain intragenic histone 3 lysine 36 trimethylation (H3K36me3) and those that do not, even though Drosophila doesnât display CpG density bimodality or methylation. We confirm that a significant number of CpG-poor genes in N. vectensis, C. intestinalis, A. mellifera and B. mori are orthologs of H3K36me3- rich genes in Drosophila. We propose that over evolutionary time, gene-body H3K36me3 has influenced gene-body DNA methylation levels, and consequently the gene-body CpG density bimodality characteristic of invertebrates that harbor CpG methylation. Overall design: Examination of DNA methylation in Apis Mellifera spermxref:PubMed:21940836ENAfalseApis melliferaComparative methylomics reveals gene-body H3K36me3 in Drosophila predicts DNA methylation and CpG landscapes in other invertebrates2025-09-242013-05-31PRJNA140771GSE29982746021940836