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DNA Methylation Involved in Epigenetics That Crown Queen Bee

NEW YORK (GenomeWeb News) – New research is revealing the epigenetic mechanism that destines some honey bees to become workers and others queens.
Genetically identical honey bee (Apis mellifera) larvae can become physiologically and behaviorally distinct adults depending on what they are fed during development. In a study published online today in Science, Australian researchers found that decreasing DNA methylation during larval development ups the chances of producing a queen. Their results suggest that nutritional cues — namely the infamous “royal jelly” that’s fed to future queens — alter methylation profiles and, subsequently, gene expression. 
“Royal jelly seems to chemically modify the bee’s genome by a process called DNA methylation and disrupts the expression of genes that turn young bees into workers,” senior author Ryszard Maleszka, a biologist at the Australian National University, said in a statement.
Honey bees are a so-called eusocial species that show a reproductive division of labor, with some members — usually the queen bees — reproducing and others doing the hive’s work. Although they have identical genes, most larvae end up becoming non-reproductive workers. Just a few become queen bees. Their secret: royal jelly.
A group of bees called nurse bees, the workers involved in brood care, feed the mysterious goo to a select few larvae, while the rest get standard provisions. Consequently, workers and queens differ in everything from appearance and physiology to life span and behavior.
Because DNA methylation can influence gene expression, Maleszka and his colleagues speculated that it might be involved in the development of distinct adults from carbon copy genomes. In an effort to assess this, the researchers used siRNA to silence an enzyme called Dnmt3, a DNA cytosine-5-methyltransferase that assists in DNA methylation on cytosine residues. Specifically, they injected one group of larvae with Dnmt3 siRNA and another with a control siRNA.
Interestingly, silencing Dnmt3-associated DNA methylation mimicked royal jelly’s effect. Nearly three quarters — 72 percent — of the larvae with reduced Dnmt3 expression were queen-like, with fully developed ovaries. On the other hand, 77 percent of those injected with control siRNA became workers.
“The ovaries of siRNA-induced queens are practically indistinguishable form the ovaries of a virgin queen reared in the hive on pure royal jelly,” the authors wrote.
The team then honed in on a single gene, dynactin p62, comparing the methylation status of its cytosine residues in tissues from the heads of queen larvae or worker larvae during development. Previous research indicates that dynactin p62 expression is up-regulated in larvae who shall be queens. Consistent with these results, the new study suggests that dynactin p62 methylation decreases in queens.
Finally, when the researchers compared control and siDnmt3-injected larvae using honey bee microarrays, they found a number of gene expression differences between the two. These included changes in genes associated with everything from hormonal regulation and intracellular signaling to protein turnover and energy-related processes. There were also differences in genes with yet-unknown functions.
More research is needed to hone in on the specific pathways affected by DNA methylation as well as the ingredients in royal jelly that mediate these epigenetic changes. But the results provide new insight honey bee epigenetics.
Apis mellifera DNA methylation is a key component of an epigenetic network controlling a most important aspect of eusociality, the reproductive division of labour,” the authors wrote. “Further work is required to unravel the causal relationship between diet-induced methylation changes and altered gene expression.”

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