Understanding the role of epigenetics in human variation – let’s start with honeybees?

Painting by Edvard Munch

 

When you next walk up the street, take a look at the faces of passers by.  Even a casual glance will reveal the enormous variation in facial characteristics – hair colour and how the hair grows, the set of the eyes, the size and shape of the nose.  These are just a few of the more obvious differences and they are outward manifestations of the great variation that exists in many human traits.  Each person is a unique product of their own “nature” and “nurture”.  By “nature”, I mean their genetic make up, the set of genes laid down as DNA in their chromosomes.  By “nurture” I mean everything else that influences how we are – our family environment, what we eat, how much exercise we take, whether we smoke and so on.

File:Identical Twins, Roselle, New Jersey, 1967.jpg
Identical twins by Diane Arbus

This very evident variation between almost all humans is one reason, I think, why identical twins are so fascinating.  Here we are confronted with two people who look very similar if not identical and this raises all sorts of questions about human individuality.  You will probably tell me that identical twins should look the same as they have the same or very nearly the same genetic make up.  This is indeed true as they derive from a single fertilised egg that divides with the two identical halves implanting and developing as separate foetuses.  If you look carefully, however, you see that “identical “ twins are not identical and they become less alike as they age.  How could this be, given that they have almost identical genes?

Here we enter the realm of a relatively new science called epigenetics.   In our chromosomes we find a set of genes (about 21,000), composed of DNA and each coding for a cellular protein building block.  The genes have, in the past, been likened to blueprints for building cells but if the genes are the only determinants of how we are then identical twins should be truly identical.  Epigenetics tells us that there can additionally be chemical tags added to the genes that change how they are expressed.  It is these epigenetic changes that underpin the differences between identical twins.

There are several different kinds of modifications that contribute to this chemical tagging but the one I want to focus on here is called methylation.  This is the addition of a small chemical tag to part of the DNA in a gene.  This affects the way the gene is expressed leading to changes in the structure of cells and ultimately in human characteristics.  We might liken these epigenetic changes to the pedals on a piano.  The pedals on a piano change the way a note sounds (soft, sustain) and this is a bit like the addition of an epigenetic marker changing how a gene is expressed.

Scientists want to study the mechanisms of epigenetics and how epigenetics contributes to human variation.  Humans are, however, far too complex so they look for tractable “model” systems.  The hope is that the model system will allow scientists to obtain answers to basic questions about epigenetics and the outcomes can then be tested in humans.  One excellent model system is provided by the honeybee and recent research has illuminated mechanisms of epigenetics in this social insect.

Honeybee society is both complex and well structured.  In a colony of honeybees, there will usually be one queen, distinguished by her greater size and, once mated, her ability to lay fertilised eggs.  These eggs grow in to larvae that are nurtured by “nurse” bees.  All larvae are initially fed Royal Jelly and if this continues they will develop in to new queens.  Most larvae are switched away from Royal Jelly to consume nectar and pollen and become worker bees that are smaller than the queen and perform various tasks within and without the hive.  They begin their lives cleaning, nursing etc. in the hive.  Later on they become foragers for nectar and pollen.  The nurse/forager transition occurs in the same insect with the same complement of genes, so it must depend on epigenetics.    Because there is such a profound change in behaviour that must depend on epigenetic changes, the honeybee is a very attractive model for studying the interplay between behaviour and changes in DNA in an organism.

Researchers in the US have recently reported results using the honeybee model to look at epigenetic changes in the brains of worker bees when they switch from nurse to forager and back again.  They tracked the methylation status of genes in the brains of honeybees.  First they took nurse and forager bees from a hive and analysed the DNA in their brains.  Comparison of the DNA methylation signatures of nurse and forager bees identified a hundred or so genes with differences in methylation tags.  Next they wanted to see if this was a reversible difference.  To investigate this, they removed all the nurse bees from a hive so that when foragers returned, some of them reverted to nurses.  When the foragers reverted to nurses the methylation state of just over a hundred genes changed.  About half of these genes overlapped with those identified in the nurse/forager comparison experiment.  For a group of about 50 genes, therefore, methylation state switches reversibly as nurse/forager behaviour switches.  This does not prove causality but it strongly suggests that the epigenetic (methylation) changes are linked to the behavioural change.  This is the first time that a complex behavioural pattern in bees has been related to changes in epigenetic tags.

The next step is to try to analyse the mechanisms behind these effects in honeybees.  The genes undergoing reversible epigenetic change are in many cases genes involved in regulation of other genes.  This tells us that we have a complex network of gene regulation leading to changes in behaviour.  It will be a major task to understand the complexity behind this.

The wider implications of the study relate to the importance of epigenetic changes in humans.  Identical twins are only one example of the effects of epigenetic changes on human behaviour.  It is thought that many human traits including the stress response, mood disorders, learning and memory involve interaction between genetics and epigenetics.

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