Generation game: not all choices are expunged from the germ line (Image: Nick Dolding/Getty)

For the first time, scientists have discovered a mechanism in humans that could explain how your lifestyle choices may impact your children and grandchildren’s genes.

Mounting evidence suggests that environmental factors such as smoking, diet and stress, can leave their mark on the genes of your children and grandchildren. For example, girls born to Dutch women who were pregnant during a long famine at the end of the second world war had twice the usual risk of developing schizophrenia. Likewise, male mice that experience early life stress give rise to two generations of offspring that have increased depression and anxiety, despite being raised in a caring environment.

This has puzzled many geneticists, as genetic information contained in sperm and eggs is not supposed to be affected by the environment, a principle called the August Weismann barrier.


But we also know the activity of our own genes can be changed by our environment, through epigenetic mechanisms . These normally work by turning a gene on or off by adding or subtracting a methyl group to or from its DNA. These methyl groups can inactivate genes by making their DNA curl up, so that enzymes can no longer access the gene and read its instructions.

Such epigenetic mechanisms are high on the list of suspects when it comes to explaining how environmental factors that affect parents can later influence their children, such as in the Dutch second world war study, but just how these epigenetic changes might be passed on to future generations is a mystery. Although there is evidence from mice that these changes can be inherited, classical genetics says this shouldn’t be possible because epigenetic marks on sperm and eggs are wiped clean after fertilisation. But now, for the first time, researchers have observed some human genes evading this clean-up process.

Escaping genes

Azim Surani at Cambridge University and colleagues have demonstrated that some genes in the developing fetus escape the cleaning mechanism.

Surani’s team analysed methylation patterns in a type of fetal cell that later forms a fetus’s own sperm or eggs. We would expect these cells to have been wiped clean when the fetus’s epigenome was reset at the early embryo stage. “However, about 2 to 5 per cent of methylation across the genome escaped this reprogramming,” says Surani.

Any methylation in these areas of the genome might therefore impact future generations – and could provide the missing clue for how a person can pass on hereditary changes caused by their environment to their children and grandchildren.

Schizophrenia and obesity

Because this is only a small proportion of the genome, Surani says most epigenetic changes brought about by our environment are very unlikely to affect future generations, but that there may be a small window of opportunity for some of these to be passed on.

A closer look at these “escapees” showed they were mostly genes implicated in brain conditions such as bipolar disorder and schizophrenia, as well as genes involved in metabolic disorders such as obesity.

Surani says he is cautious about drawing any further conclusion as to whether or not these have any functional significance for the health of future generations until they have discovered more about how these genes manage to evade reprogramming and why.

Marcus Pembrey, emeritus professor of paediatric genetics at University College London’s Institute of Child Health, says that the escapees look very intriguing. Although there is a long way to go in our understanding of transgenerational effects, “I think we can say the August Weismann barrier has been well and truly breached,” he says.

Journal reference: Cell, DOI: 10.1016/j.cell.2015.04.053