DNA methylation is a very small molecule. It's a methyl group that's added to the cytosine. It can also be added to adenine in bacterial systems, but it's a very, very small molecule that's added to the cytosine, and it doesn't alter the DNA in any way, but produces this little tiny functional group on top of DNA, and a lot of enzymes, a lot of proteins can be rejected as a result of this methyl group being put on, and then we have whole sets of enzymes and proteins that actually look at and bind to that methyl group.
So, it's a very small modification. It's so-called the fifth base, and hydroxymethylation, that we were talking about before, is sometimes called the sixth base, because it's cytosine, but it's been changed and altered very, very minimally by a methyl group or a hydroxymethyl group, and these are covalent changes, so that once a cytosine is methylated, it's very difficult to remove that methyl group enzymatically. It's almost impossible. So, once DNA is methylated, it stays methylated.
Well, honeybees is an extremely interesting example of epigenetic changes that occur. A hive of honeybees has one genetic sequence. They're all clones of each other. They're all clones of the queen. So, identical sequences, but what differentiates male drones, from the queen, from worker bees, and remember that the worker bee, and a drone bee, and a queen bee, have very different roles in the hive. Obviously, the queen is laying the eggs. She lasts up to three years in a hive, so she overwinters. The drone bees, for example, only live for a very short period of time, and they're basically a sperm on wings. So, again, same genetics, but different morphologies, different actions, and different things that they do.
A worker bee, on the other hand, starts out life taking care of the brood, and then goes off and flies, and collects nectar, collects pollen, and all of these other things, so the differences between queens, and drones, and worker bees is very different in their roles in the hive, yet their DNA is identical to each other. So, what changes have happened to this DNA, that creates these differences in all of these things? The changes are epigenetic. It's DNA methylation. It's DNA modification that has turned off certain genes in these worker bees, turned off certain genes in these drones, but in the queen, all genes are active, so methylation has been removed.
During times of stress or times that the hive has determined that we need another worker, or another queen, workers will start feeding a normal egg the substance called royal jelly. Royal jelly has so many different compounds, but one of the compounds that we believe is in royal jelly is that it inhibits a enzyme called Dnmt1-methyltransferase. Dnmt1-methyltransferase methylates DNA, well, in all mammalian systems or insect systems as well. So this royal jelly is being added to these eggs during development, and it demethylates a whole subset of genes in the egg, and then the egg becomes a queen as a result. So, this is a great example, like I said, of feeding something food and food changing the epigenetic signature during development, changing the DNA methylation pattern during development, in this case removing the DNA, removing the methylation from the DNA.
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