Chapter 3. Life As We Knew It
A poet can survive everything but a misprint.
If we are going to understand epigenetics, we first need to understand a bit about genetics and genes. The basic code for pretty much all independent life on earth, from bacteria to elephants, from Japanese knotweed to humans, is DNA (deoxyribonucleic acid). The phrase ‘DNA’ has become an expression in its own right with increasingly vague meanings. Social commentators may refer to the DNA of a society or of a corporation, by which they mean the real core of values behind an organisation. There’s even been a perfume called after it. The iconic scientific image of the mid-20th century was the atomic mushroom cloud. The double helix of DNA had similar cachet in the later part of the same century.
Science is just as prone to mood swings and fashions as any other human activity. There was a period when the prevailing orthodoxy seemed to be that the only thing that mattered was our DNA script, our genetic inheritance. Chapters 1 and 2 showed that this can’t be the case, as the same script is used differently depending on its cellular context. The field is now possibly at risk of swinging a bit too far in the opposite direction, with hardline epigeneticists almost minimizing the significance of the DNA code. The truth is, of course, somewhere in between.
In the Introduction, we described DNA as a script. In the theatre, if a script is lousy then even a wonderful director and a terrific cast won’t be able to create a great production. On the other hand, we have probably all suffered through terrible productions of our favourite plays. Even if the script is perfect, the final outcome can be awful if the interpretation is poor. In the same way, genetics and epigenetics work intimately together to create the miracles that are us and every organic thing around us.
DNA is the fundamental information source in our cells, their basic blueprint. DNA itself isn’t the real business end of things, in the sense that it doesn’t carry out all the thousands of activities required just to keep us alive. That job is mainly performed by the proteins. It’s proteins that carry oxygen around our bloodstream, that turn chips and burgers into sugars and other nutrients that can be absorbed from our guts and used to power our brains, that contract our muscles so we can turn the pages of this book. But DNA is what carries the codes for all these proteins.
If DNA is a code, then it must contain symbols that can be read. It must act like a language. This is indeed exactly what the DNA code does. It might seem odd when we think how complicated we humans are, but our DNA is a language with only four letters. These letters are known as bases, and their full names are adenine, cytosine, guanine and thymine. They are abbreviated to A, C, G and T. It’s worth remembering C, cytosine, in particular, because this is the most important of all the bases in epigenetics.
One of the easiest ways to visualise DNA mentally is as a zip. It’s not a perfect analogy, but it will get us started. Of course, one of the most obvious things that we know about a zip is that it is formed of two strips facing each other. This is also true of DNA. The four bases of DNA are the teeth on the zip. The bases on each side of the zip can link up to each other chemically and hold the zip together. Two bases facing each other and joined up like this are known as a base-pair. The fabric strips that the teeth are stitched on to on a zip are the DNA backbones. There are always two backbones facing each other, like the two sides of the zip, and DNA is therefore referred to as double-stranded. The two sides of the zip are basically twisted around to form a spiral structure – the famous double helix. Figure 3.1 is a stylised representation of what the DNA double helix looks like.
Figure 3.1 A schematic representation of DNA. The two backbones are twisted around each other to form a double helix. The helix is held together by chemical bonds between the bases in the centre of the molecule.
The analogy will only get us so far, however, and that’s because the teeth of the DNA zip aren’t all equivalent. If one of the teeth is an A base, it can only link up with a T base on the opposite strand. Similarly, if there is a G base on one strand, it can only link up with a C on the other one. This is known as the base-pairing principle. If an A tried to link with a C on the opposite strand it would throw the whole shape of the DNA out of kilter, a bit like a faulty tooth on a zip.
The base-pairing principle is incredibly important in terms of DNA function. During development, and even during a lot of adult life, the cells of our bodies divide. They do this so that organs can get bigger as a baby matures, for example. They also grow to replace cells that die off quite naturally. An example of this is the production by the bone marrow of white blood cells, produced to replace those that are lost in our bodies’ constant battles with infectious micro-organisms. The majority of cell types reproduce by first copying their entire DNA, and then dividing it equally between two daughter cells. This DNA replication is essential. Without it, daughter cells could end up with no DNA, which in most cases would render them completely useless, like a computer that’s lost its operating software.
It’s the copying of DNA before each cell division that shows why the base-pairing principle is so important. Hundreds of scientists have spent their entire careers working out the details of how DNA gets faithfully copied. Here’s the gist of it. The two strands of DNA are pulled apart and then the huge number of proteins involved in the copying (known as the replication complex) get to work.
Figure 3.2 shows in principle what happens. The replication complex moves along each single strand of DNA, and builds up a new strand facing it. The complex recognises a specific base – base C for example – and always puts a G in the opposite position on the strand that it’s building. That’s why the base-pairing principle is so important. Because C has to pair up with G, and A has to pair up with T, the cells can use the existing DNA as a template to make the new strands. Each daughter cell ends up with a new perfect copy of the DNA, in which one of the strands came from the original DNA molecule and the other was newly synthesised.
Figure 3.2 The first stage in replication of DNA is the separation of the two strands of the double helix. The bases on each separated backbone act as the template for the creation of a new strand. This ensures that the two new double-stranded DNA molecules have exactly the same base sequence as the parent molecule. Each new double helix of DNA has one backbone that was originally part of the parent molecule (in black) and one freshly synthesised backbone (in white).
Even in nature, in a system which has evolved over billions of years, nothing is perfect and occasionally the replication machinery makes a mistake. It might try to insert a T where a C should really go. When this happens the error is almost always repaired very quickly by another set of proteins that can recognise that this has happened, take out the wrong base and put in the right one. This is the DNA repair machinery, and one of the reasons it’s able to act is because when the wrong bases pair up, it recognises that the DNA ‘zip’ isn’t done up properly.
The cell puts a huge amount of energy into keeping the DNA copies completely faithful to the original template. This makes sense if we go back to our model of DNA as a script. Consider one of the most famous lines in all of English literature:
O Romeo, Romeo! wherefore art thou Romeo?
If we insert just one extra letter, then no matter how well the line is delivered on stage, its effect is unlikely to be the one intended by the Bard: