DNA methylation dynamics, metabolic fluxes, gene splicing, and alternative phenotypes in honey bees

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 13; pp. 4968 - 4973
• Main Authors: Foret, Sylvain, Kucharski, Robert, Pellegrini, Matteo, Feng, Suhua, Jacobsen, Steven E., Robinson, Gene E., Maleszka, Ryszard
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 27.03.2012; National Acad Sciences
• Subjects: adults; Aging; Aging - genetics; Alternative splicing; Animals; Antisense; Apis; Apis mellifera; Bees; Bees - genetics; Biological Sciences; Brain; Caste determination; Citric Acid Cycle; Citric Acid Cycle - genetics; Data processing; Deoxyribonucleic acid; Development; Diet; Dietary intake; DNA; DNA methylation; DNA Methylation - genetics; DNA methyltransferase; DNA-directed RNA polymerase; Exons; Feeding; Gene Expression Profiling; genes; Genes, Insect; Genes, Insect - genetics; Genetics; Genotype & phenotype; Head; Hierarchy, Social; Honey; Honey bees; Hormones; Insect castes; Insect genetics; Insect larvae; Insect Proteins; Insect Proteins - genetics; Insect Proteins - metabolism; Insulin; Juvenile hormones; Larva; Larva - genetics; Larvae; Larval development; Lymphoma; metabolic flux; Metabolic Networks and Pathways; Metabolic Networks and Pathways - genetics; Metabolism; Methylation; methyltransferases; Models, Genetic; Molecular Sequence Annotation; Nodes; nutrition; Organ Specificity; Organ Specificity - genetics; Phenotype; Proteasome Endopeptidase Complex; Proteasome Endopeptidase Complex - metabolism; Protein-tyrosine kinase; Queen honey bees; Queens; RNA Splicing; RNA Splicing - genetics; RNA-protein interactions; Royal jelly; Signal Transduction; Signal Transduction - genetics; Spliceosomes; Spliceosomes - metabolism; Transcription; Ubiquitin; Ubiquitin - metabolism; Workers
• DOI: 10.1073/pnas.1202392109
• ISSN: 0027-8424; 1091-6490

In honey bees (Apis mellifera), the development of a larva into either a queen or worker depends on differential feeding with royal jelly and involves epigenomic modifications by DNA methyltransferases. To understand the role of DNA methylation in this process we sequenced the larval methylomes in both queens and workers. We show that the number of differentially methylated genes (DMGs) in larval head is significantly increased relative to adult brain (2,399 vs. 560) with more than 80% of DMGs up-methylated in worker larvae. Several highly conserved metabolic and signaling pathways are enriched in methylated genes, underscoring the connection between dietary intake and metabolic flux. This includes genes related to juvenile hormone and insulin, two hormones shown previously to regulate caste determination. We also tie methylation data to expressional profiling and describe a distinct role for one of the DMGs encoding anaplastic lymphoma kinase (ALK), an important regulator of metabolism. We show that alk is not only differentially methylated and alternatively spliced in Apis, but also seems to be regulated by a cis-acting, anti-sense nonprotein-coding transcript. The unusually complex regulation of ALK in Apis suggests that this protein could represent a previously unknown node in a process that activates downstream signaling according to a nutritional context. The correlation between methylation and alternative splicing of alk is consistent with the recently described mechanism involving RNA polymerase II pausing. Our study offers insights into diet-controlled development in Apis.