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ScienceWise - Winter 2012

Royalty is not in the blood

Article Illustration
The bee is a perfect example of epigenetics in action

What epigenetics in bees can tell us about human health

Over the past few decades there have been great leaps made in our ability to map and interpret the DNA sequences that make up the genome of many organisms, including humans. It’s led to a common perception is that one’s genome will dictate every aspect of one’s life, from longevity and disease to success or failure in any given endeavour. Movies like Gattaca explore what might happen if this unshakable faith in the pre-destiny of genetics were taken to extremes in human society.

However as is so often the case in science, the real story is far more complicated that the hype. Although genes are undeniably crucial in shaping an organism’s development, their expression can be changed dramatically by environmental factors. A phenomenon known as epigenetics.

Professor Ryszard Maleszka from the ANU Research School of Biology is one of the world’s foremost authorities on the epigenetics of honey bees. “Within the honey bee you have a perfect example of epigenetics at work,” Professor Maleszka says. “Every bee in the hive has an identical genome yet drones (male bees), queens and workers are very different organisms. For example, the Queen is larger, she’s fertile, and she has vastly greater longevity that the workers.”

What triggers this change during the development of the larvae is a substance known as royal jelly. If a larvae is fed with royal jelly it will develop into a queen, if fed on honey and sugar it will become a worker. You might be tempted to think this is just a case of a better fed baby growing fatter than a malnourished one, but it’s not. The queen has major physiological differences such as special membranes that are resistant to oxidation damage (which probably explains her longevity), and she has large ovaries whereas workers have none.

The turning point in larva development occurs at about four days. If the larva is fed on royal jelly for just four days it will become a queen. No amount of royal jelly will turn an older larva into a queen and no subsequent deprivation of jelly will stop a four day old queen developing into her adult form.

But how can these dramatic epigenetic development changes occur when the nature of an organism is hard wired into its DNA?

The answer lies in a process called methylation. The DNA code is comprised of four building block molecules known as base pairs. Different patterns of these pairs along the DNA strand constitute different genes. During methylation a molecule with a methyl group attaches itself to one of these base pairs (usually cytosine). This doesn’t damage or alter the DNA itself but it does effectively switch off aspects of a particular gene’s expression.

Substances in royal jelly inhibit methylation of “worker” genes in the bee larvae allowing the organism to develop into a queen. Professor Maleszka’s research group proved this to be the case by using a methylation inhibiting compound on larvae that were fed only on honey. With inhibited methylation, the majority of the larvae developed into queens even without royal jelly.

“Usually in science things are far more complicated than we first imagine and often when we test an idea the results aren’t as clear as we’d like,” Professor Maleszka says, “So when we ran these experiments and all the queens developed from larvae in which methylation was inhibited it seemed too good to be true!”

Although this work is interesting in its own right, it also has far reaching implications for human health. The DNA methylation mechanism in bees is the same as that in humans and it’s know that methylation plays an important role in many diseases including cancer.

“We really need to begin looking beyond the fixed genome to understand many of the current health problems society faces like obesity and diabetes,” Professor Maleszka explains, “There are rarely single genes that code for a given disease, it’s more like a complex network of gene expression that’s heavily modified by environmental factors.”

“The reality of epigenetics is fairly obvious if you think about it. Every cell in the human body has the exact same DNA yet there are many very different types of cells such as nerve, bone, muscle. Epigenetic factors usually in the embryonic stage, dictate these quite different development paths. Likewise it’s becoming increasingly obvious that environmental factors such as diet will have a huge bearing on the ultimate health outcomes for an individual.”

These environmental factors make the interpretation of a genome test on an individual more difficult. For example, even though a DNA test may tell you that you have genes susceptible to lung cancer whether or not you ultimately develop that cancer depends on environmental factors. If you smoke two packets of cigarettes a day even good genes might not save you, whereas if you eat well and never smoke, you might have terrible genes and still remain perfectly healthy.

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