How your behaviour can change your children’s DNA
New research into inheritance shows we can alter family traits for better or for worse.
Jonathan Leake reports
For Beatrix Zwart being young means having fun. She works hard, and out of hours she plays hard — including plenty of nights on the town with her friends.
“I lead a similar lifestyle to a lot of young professionals in Britain and I don’t intend to have any children until I’m well into my thirties,” said Zwart, a 25-year-old Belgian who lives in London.
“I’ve never really thought my lifestyle now could have any effect on my future children or grandchildren.”
Until recently that would also have been the opinion of most scientists. Genes, it was thought, were highly resilient. Even if people did wreck their own DNA through bad diet, smoking and getting fat, that damage was unlikely to be passed to future generations.
Now, however, those assumptions are being re-examined. At the heart of this revolution is a simple but controversial idea: that DNA can be modified or imprinted with the experiences of your parents and grandparents.
According to this new science, known as epigenetics, your ancestors’ diet, smoking habits, exposure to pollutants and levels of obesity could be affecting you today. In turn, your lifestyle could affect your children and grandchildren. For Zwart and millions of others choosing to delay parenthood this raises new moral questions. What effect, for example, will nights spent in wine bars have on their descendants? Will cigarettes smoked today compromise the health of grandchildren? If they become obese is that their right, or does it impose a burden of ill-health on generations yet unborn?
Some of the answers may be emerging. There is, for example, evidence that the recent surge in diseases such as diabetes, obesity and heart disease is partly linked to the lifestyles of past generations.
Last week academics at Baylor College of Medicine in Houston, Texas, published research showing that overweight mothers produce offspring who become even heavier, resulting in the spread of obesity across the generations. “There is a worldwide obesity epidemic,” said Robert Waterland, a professor of paediatrics who led the study. “Why is everyone getting heavier and heavier? One hypothesis is that maternal obesity before and during pregnancy causes epigenetic changes in the ways genes are expressed.”
Waterland’s research was done in mice for ethical reasons but population studies have suggested similar effects in humans.
Marcus Pembrey of the Institute of Child Health at University College London identified 166 fathers who admitted smoking before they were aged 11, and whose sons had a sharply elevated risk of obesity. The implication was that smoking had altered the way their genes worked without actually changing the genes.
In another study Pembrey and colleagues analysed records of an isolated Swedish community to find that men whose grandfathers had experienced childhood food shortages tended to live longer. They too appeared to have inherited a change in the way their DNA worked — this time a beneficial one.
Researchers had long suspected that DNA may not be the only means of inheritance. They knew that diseases such as cancer, heart disease and diabetes ran in families, but in complex patterns that seemed to defy traditional genetics. What they lacked were the instruments to peer into cells and see what was happening.
What’s more, other scientists saw such ideas as heretical, amounting to an attack on the evolutionary theories of Charles Darwin and the laws of genetic inheritance outlined by Gregor Mendel, two of the cornerstones of modern biology.
The next year will witness a rash of celebrations for the bicentennial of Darwin’s birth. It will also see publication of a number of academic papers on novel forms of inheritance.
Steve Jones, professor of genetics at University College London, said: “The evidence is increasingly that environmental factors like diet or stress can affect organisms in ways that are transmitted to offspring without any changes to DNA.”
Such apparent conflicts can be resolved but only by finding out what is happening at the level of DNA molecules — the basic building blocks of life — and scientists have never had that power until now.
“The technologies for epigenetics arose from the human genome project and have only become widely available within the last few years,” said Stephan Beck, professor of medical genomics at the Cancer Institute, University College London. “That is what makes it so exciting.”
A key finding is that although DNA molecules control almost everything that happens in a cell, each molecule contains far more information than any single cell needs.
A liver cell, for example, has no need for the genes that govern sperm production, while a brain cell that started generating, say, hair or nails could be positively dangerous.
This means that in every cell some genes are turned on but many more are “trussed up” and neutralised by a host of smaller molecules. The change, then, is not to the DNA itself but to the “switches” that turn the genes on or off.
The system that oversees this process, the epigenome, is meant to be flexible enough for such genes to be brought in and out of play as needed. Sometimes, however, it goes wrong.
For example, a research group from Toronto’s Centre for Addiction and Mental Health looked for differences in post-mortem tissue taken from the brains of 35 men suffering from schizophrenia, a disease that runs in families but without any clear pattern. They found epigenetic changes affecting 40 or so key genes involved in brain function.
“The brain is particularly susceptible to epigenetic changes, especially during development,” said Dr Jonathan Mill, a lecturer in psychiatric epigenetics at the Institute of Psychiatry who was involved with the research. “That is why pre- natal exposure to alcohol or other toxins may have such a strong effect.”
For humans perhaps the most important finding of epigenetics is that we are not owners of our genes but their guardian. If we drink heavily, take drugs, get fat or wait too long to reproduce, then epigenetics might start tying up some of the wrong genes and loosening the bonds on others. Sometimes those changes will affect sperm and egg cells.
One of the clearest pieces of evidence for such changes emerged from the work of Avi Reichenberg, also of the Institute of Psychiatry. He found children born to fathers aged 40-plus were almost six times more likely to have autism than those born to fathers under 30 and that the effect appeared to be epigenetic.
In a society where people have children later in life, such effects have huge medical and social implications, suggesting that people putting off parenthood should be looking after their DNA.
Zwart is on the right track: recently she started a twice-a-week exercise regime, something for which any future children and grandchildren may well have cause to thank her.
http://www.timesonline.co.uk/tol/life_a ... 364054.ece
