SciWhys: What is gene mutation?

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This is the latest post in our regular OUPblog column SciWhys. Every month OUP editor and author Jonathan Crowe will be answering your science questions. Got a burning question about science that you’d like answered? Just email it to us, and Jonathan will answer what he can. Today: what is gene mutation?

By Jonathan Crowe

In my last three posts I’ve introduced you to the world of biological information, taking you from the storage of biological information in libraries called genomes, which house information in individual books called chromosomes (themselves divided into chapters called genes), to the way the cell makes use of that stored information to manufacture the molecular machines called proteins.

But what happens when the storage of information goes wrong? If we’re reading a recipe and that recipe contains a mistake, chances are that the end-result of our culinary endeavour won’t end up as it should. And so it is at the level of cells. If the information the cell is using is somehow wrong, the end result will also be wrong – sometimes with catastrophic results.

I’ve mentioned in previous posts how biological information is captured by the sequence of the building block ‘letters’ from which DNA is constructed. The sequence of letters is ultimately deciphered by a molecular machine called the ribosome, which reads the sequence of letters in sets of three, and uses each trio to determine which amino acid – the building block of proteins – should be used next in its mission to construct a particular protein. It should come as no surprise that, if the recipe for the protein is changed – if the sequence of DNA ‘letters’ is altered – the protein that is manufactured will probably contain errors as a result. And if a protein contains errors, it won’t be able to function correctly, just as flat-packed furniture will end up being decidedly wobbly if you construct it from the wrong parts.

Imagine a snippet of DNA has the sequence GGTGCTAAG. The ribosome would ‘read’ this sequence, and would use it as the recipe for building a chain of three amino acids: Glycine-Alanine-Lysine. Now imagine that we alter just one letter in our original sequence so that it becomes GGTCCTAAG. All we’ve done is swap a G for a C at the fourth position in the DNA sequence. However, this change is sufficient to affect the composition of the protein that is produced when the sequence is deciphered: the ribosome will now build a chain with the composition Glycine-Proline-Lysine.

Surely such a small change won’t actually cause significant problems in a cell, though. Right? Wrong. Amazingly (and perhaps unnervingly) the tiniest error can have really quite significant consequences.

Let’s take just one example. Sickle cell anaemia is a condition that affects the red blood cells of humans.  Red blood cells fulfil the essential role of transporting oxygen from our lungs to all the living cells of our body: they continually circulate through our arteries and veins, shuttling oxygen from one place to another. A healthy red blood cell looks a bit like a ring doughnut (though it doesn’t actually have a hole right through the middle); by contrast, the red blood cells of individuals with sickle cell anaemia become warped into crescent-like shapes (like a sickle, the grass-cutting tool, after which the disease is named). These sickle cells no longer pass freely through our arteries and veins. Instead, they tend to get entangled with each other. As a result, the flow of oxygen round the body is impeded, and the individual afflicted with the disease can suffer breathlessness, dizziness, and sudden pain throughout the body as a result.

So what has this to do with changes in the sequence of a gene? Almost unbelievably, this debilitating disease is caused by just a single error in the sequence of a particular gene. The gene in question (one particular ‘chapter’ in one of our chromosomes, the genetic ‘books’ that make up our genome ‘library’) is constructed from a total of 625 building block letters. Yet, a change in just one of those letters – from the letter A to T – results in the amino acid valine being added in place of the amino acid glutamic acid at a particular point in the protein haemoglobin – the part of the red blood cell to which oxygen actually attaches – as it is constructed from the recipe that the gene spells out. This change is all that’s needed to affect the structure of the haemoglobin, which, in turn, affects the shape of the red blood cell in which it is found, causing it to adopt the distorted sickle shape.

Why do such errors happen in the first place? In short, because cells have to make copies of their genomes – and no process of copying is completely error-free. Almost every cell in our body must possess a full library of biological information – a complete copy of our genome. So, every time a cell divides to produce two daughter cells (when our skin cells divide to repair a cut or graze, or the cells of our stomach lining are replenished, for example) it must first make a copy of its genome so that each daughter cell ends up with a full genome. But as the cell copies its genome – literally letter by letter – mistakes creep in. (If you were to re-type this post without using the delete key as you typed, how many errors do you think there would be in the end result? I’m writing this on a laptop that’s just a few months old, and I can already see that the delete key is the most worn key on the keyboard!) These mistakes are what we call mutations.

Fortunately for us, however, the introduction of errors during the genome-copying process is a rare event: the cells of our bodies do a truly remarkable job of keeping things error-free. Indeed, they copy DNA with an accuracy of 99.999% – this means that only one error is introduced for every 100,000 letters that are copied. That’s no mean feat – and is thanks to a particular molecular ‘editor’ that proof-reads the DNA as it is being copied, spotting errors and correcting them as it reads.

Hiccups in the copying of DNA by our cells are not the only cause of gene mutations: various environmental factors can cause them too. The most prevalent of these is ultra-violet light, a natural component of sunlight – but a component that can cause unwanted changes in the chemical structure of DNA when it comes into contact with our cells. The effect of ultra-violet light on our DNA is the reason why we’re encouraged to wear sunscreens when we’re out basking in the sun: you might think a tan will make you look healthy, but the cost might be the creation of an error in the DNA of some of your skin cells that triggers the formation of a skin tumour. Is that a price worth paying for a few weeks of looking bronzed?

Despite this, gene mutation itself isn’t necessarily a bad thing. Indeed, if mutations weren’t to occur, we’d not see around us the remarkable diversity of life that we do. For gene mutation is the molecular ‘fuel’ for the process of evolution, as I’ll explore in a future post.

Jonathan Crowe is Editor in Chief for Natural, Health & Clinical Sciences in the Higher Education Department at Oxford University Press. A biochemistry graduate, he manages OUP’s undergraduate textbook publishing programme across a range of science and science-related disciplines. He is also an author of Chemistry for the Biosciences, now in its second edition, and was a runner-up in the Daily Telegraph/BASF Young Science Writer Awards (in 2001, when he was still classed as being ‘young’). You can read more about OUP’s science books here.

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