Stress response spans generations

Scientists have shown that the effects of stress can be passed from one generation to the next via chemical changes to the DNA which turn genes on or off without altering the code itself.

Researchers from the RIKEN Tsukaba Institute in Ibraka, Japan, exposed fruit flies to two different types of stress: heat or salty water. This led to alterations in the packaging of their DNA, resulting in genes which were normally turned off being turned on. These sorts of modifications are known as epigenetic changes. The scientists then looked at the offspring of the stressed fruit flies and saw the same changes in DNA packaging and gene activation, even though this generation of flies had not been exposed to stress themselves.

The idea that the effects of stress can be inherited through epigenetic change is hotly debated among geneticists. Professor Shunsuke Ishii who led the study told New Scientist: 'We believe we can convince many sceptics by clarifying this mechanism'.

The work, published in the journal Cell, focussed on a protein called Drosophila activating transcription factor-2 (dATF-2). Under normal circumstances dATF-2 attaches to the DNA keeping it tightly bound so that surrounding genes are turned off. When the fruit flies are exposed to stress the dATF-2 protein detaches, which allows the DNA to uncoil causing the genes to be activated.

The study found that the uncoiled state of the DNA was passed on to the offspring, with coiling being restored by the third generation. Furthermore, when two successive generations of fruit fly were exposed to stress the uncoiling of DNA was seen into the fifth generation, although it reverted back by the sixth. This suggests that multi-generational exposure to stress has a longer-lasting impact than an exposure in just one generation.

'What’s really exciting is that this study shows a clear molecular mechanism that responds to stress and results in a change in chromatin state in the germ line', Professor Moshe Szyf of McGill University, Canada, said in an interview with New Scientist. 'This is a first, to my knowledge'.

The mammalian equivalent of dATF-2 is called ATF-7. Previous work by Professor Ishii and his team showed that psychological stress in mice similarly alters the ATF-7 protein and DNA packaging, although work is still underway to establish whether these changes are inherited in subsequent generations. The scientists have speculated that, if stress has the same effect on the ATF-7 protein in humans, this research could lead to a better understanding of a range of complex disorders.