Methionine as a methyl donor regulates caste differentiation in the European honey bee (Apis mellifera)

Nutrition contributes to honey bee caste differentiation, but the role of individual nutrients is still unclear. Most essential amino acid contents, except that of methionine (Met), are greater in royal jelly than worker jelly. After ∼3.5 d, the Met content in the latter was slightly greater than in the former. Met is the major raw material used in the synthesis of S-adenosyl-L-methionine, an active methyl donor for DNA methylation, which is an epigenetic driver of caste differentiation. Here, we tested whether Met regulates caste differentiation in honey bees by determining its effects on the caste development of bees receiving four diets: the basic, basic + 0.2% Met, basic + 0.2% Met + 20 mg/kg 5-azacytidine, and basic + 20 mg/kg 5-azacytidine. The presence of Met decreased the adult bee body length and the numbers of ovarioles, indicating that Met may direct the development of female larvae toward worker bees. The upregulated expression of SAMS, Dnmt1, and Dnmt3 caused by Met exposure in 4-d-old larvae indicated that the worker-inductive effects of Met may occur through the promotion of DNA methylation. We investigated the co-effects of Met and glucose on bee development, and found that the effects of an increased glucose level on the number of ovarioles and body length did not strengthen the worker-inductive effects caused by Met. Our results contribute to caste development theory and suggest that Met-as a methyl donor-plays a regulatory, but not decisive, role in caste differentiation.