Epigenetic anointment

Dec 23rd 2010, 16:21 by The Economist online

LIFE in the hive is nasty, brutish and short—if you are a worker bee, that is. Workers spend the 20 days or so of their adulthoods constructing honeycomb, feeding larvae, foraging for nectar and pollen beyond the hive, and never producing offspring. The queen, by contrast, lives on for years in languor, fed and preened by workers as she lays up to 2,000 eggs a day for honeybee posterity.

Yet these starkly different fates emerge from the same genome. Who becomes royal and who a drudge depends on who gets fed with a fantabulous substance called royal jelly. The jelly does this by modulating the expression of the insect’s genes, but the details have hitherto been obscure.

In a study published in PLoS Biology, Ryszard Maleszka of the Australian National University and his colleagues illuminate some of those details. One of the ways that genes are regulated is by a process called methylation. This adds chemicals called methyl groups to DNA. These then obstruct the machinery responsible for turning genetic instructions into working proteins—a phenomenon known as epigenesis. Dr Maleszka has shown that royal jelly acts, at least in part, by changing the pattern of methylation. He and his team have produced a methylation map (a “methylome”) of the DNA in honeybee brains. 

They found 561 genes whose methylation patterns were different in queens and workers. Most of these genes encode humdrum proteins that regulate a cell’s metabolism or transmit molecular signals that keep it ticking over. Differences in these genes presumably explain the different body sizes and lifespans of queens and workers. A few of the affected genes, though, are involved in brain development and signalling between nerve cells. These would explain differences in behaviour.

A recurring theme was that the epigenetic marks found can pick and choose from alternative options offered by the genome. Genes are divvied up into pieces that may be swapped in or out of the final instructions for making a protein, allowing a cell to       fine-tune a protein to its needs. Queens and workers differed in how methyl tags were clustered at the splicing sites between these pieces. For example, the splicing sites of the gene needed to make the short version of a protein called GB18602 (of unknown function, although its counterpart in fruit flies is involved in fat and sugar metabolism) were tagged with methyl groups in workers but not in queens. This strongly correlated with the meagre amounts of the short version of GB18602 found in workers and its abundance in queens. 

How these precise patterns of methylation arise remains a mystery, which may involve some as yet unknown guidance molecules that instruct the methylating enzyme exactly where to tag the genome. This is a crucial question for human health, too, because epigenetic marks on certain genes can spur disease (the runaway cell division that causes cancer being one important example). With a genome a tenth the size of a human’s, and less crowded with methyl tags to boot, the honey bee may lead the way to the principles behind how these epigenetic patterns emerge—and ultimately determine fates beyond the hive.