We are all mutations

Mutations – mistakes in the copying of genetic material – are not the freak events of science fiction. In fact, they are very common. Mutations occur in the cells of every individual as he or she grows older. And they are happening all the time. While you are reading this article, for example, you will have undergone tens of thousands of mutations.

“Historically people looked for mutations in fruit flies and plants, which happened very rarely,” says Steve Jones, Professor of Genetics at University College London.

“When you start looking at DNA directly, the mutation rate turns out to be very high.”

Chemistry can, to some extent, explain mutations. DNA, the molecule which codes genetic information, is very long and very complex. When it copies itself, it makes mistakes.

DNA is made up of two strands wound together in a spiral, the famous double helix discovered by scientists James Watson and Francis Crick in 1953. It replicates itself by creating two new double helices, each made up of one old strand and one new strand. Enzymes compare the strands and correct the mistakes, a process known as “proofreading”.

But these repair enzymes do not correct all the mistakes. There, as they say, is the rub. “If the repair enzymes can put 99 per cent of them right, why don’t they put all of them right? There’s a lot of argument about the evolution of the mutation rate,” says Professor Jones. Every organism passes these mistakes on to their offspring.

These mutations are very common and most seem to have very little affect on an organism’s ability to survive.

As Professor Jones says: “Are most mutations just accidental noise in the system, crackles on a radio set – they don’t make much difference? There’s a very convenient assumption that that’s true.”

When a mutation does observably change an organism, the result is, simply put, random. But that is not the whole story.

“Is it like dropping a cup?” Jones asks. “Will it shatter into a random selection of pieces, or is it in some ways directed? The short answer is that they do happen at random. There are some quite sophisticated things to suggest otherwise, but that’s so tangled a tale, it is better to imagine that they happen at random.”

So, for example, putting mice in a cold environment will not necessarily lead to offspring with thicker fur.

More often than not, mutations will hinder an organism’s ability to survive. Only now and again will mutation produce a beneficial change.

Natural selection weeds out the good from the bad. Over time the proportion of organisms with the beneficial mutated gene will increase until the gene becomes the norm in the population.

In other words, mutation offers a range of genetic variation and natural selection acts upon it.

Looked at in this way, the “mistakes” of mutation, the flaws in the system, become the keys to survival in an ever-changing world, one of the reasons myriad organisms have evolved from primordial soup.

But genetics is a young science. The significance of Gregor Mendel’s discovery of the laws of heredity was not appreciated in a genetic context until the turn of the 20th century. Watson and Crick discovered the molecular structure of DNA just over 50 years later and the mapping of the human genome was not completed until near the end of the 20th century.

Our understanding of mutation is continually evolving.

“One of the striking findings recently,” says Professor Jones, “is that the most powerful agent of mutation isn’t X-rays or chemicals in the diet, it’s the age of parents, particularly the age of fathers. Older fathers pass on much more damaged DNA than younger fathers.”

“Old”, in this case, is over 25 years old.

The mutation of any gene favours the population to the detriment of the individual, but genetics has already started to change all that.

Gene analysis promises to change it further. This brave new technology offers glimpses into how what we inherit genetically from our parents could shape our lives.

Some people’s genes strongly predispose them to breast cancer or heart disease. Knowing this information can be vital. Genetic screening tests allow individuals to pinpoint possible problems and act to reduce the risks.

One recent, well-publicised example is the case of Masha Gessen, the foreign correspondent and author. When she discovered that she carried a mutation in the BRCA1 gene that increased her probability of developing breast cancer to more than 85 per cent, she decided to have a full mastectomy to reduce the risk.

“I belong to a generation that grew up believing we were shaped by love, care, or lack of it,” she writes in her book, Blood Matters. “But now we will go to our graves believing that it is a combination of letters in our genetic code that determines how we get there and when.”

Using our genes to predict exactly how and when each of us will die is a long way off. “In general, genetics has always been the science of the extreme,” says Professor Jones. “Rare forms of breast cancer. Rare forms of heart disease.”

The gene genie does not hold all the cards. In fact much of how we age is down to lifestyle.

“The strongest predictor of your life expectancy globally is your parents’ income,” says Professor Jones. “In Britain, there is a 10-year difference in life expectancy between the poorest postcode, which is in Scotland, and the richest postcode, which is in Surrey. That is a huge difference.”

Don’t smoke. Drink less. Exercise more. Avoid fatty foods. For the moment these lifestyle choices are important in determining how long we will live and how healthy we will be.

“Once you get everybody entirely educated, eating an entirely healthy diet and wearing a seat belt,” says Professor Jones, “then the genes may become important.”

Published in The National on 13 August 2008.