Epigenetics: genes, environment and the generation game

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family_generational_cancer news_epigenetics_800x500Source: The Guardian – Angela Saini.

New research claims that environmental factors affect not just an individual’s genes but those of their offspring too. Diabetes, obesity – even certain phobias – may all be influenced by the behaviour of our forebears.

As with so much in science, this story owes a lot to mice. The tale begins with a pregnant mouse in a laboratory in Boston, Massachusetts. Such is the unfortunate lot of a lab rodent that she was kept on a near-starvation diet when she was close to giving birth. As scientists expected, her babies were born smaller than usual. When they were raised normally, they later developed diabetes.

Now comes the twist. Even though these mice were well fed, their own young were also born unusually small and with a higher risk of diabetes. This was strange, because nothing had changed genetically and they hadn’t suffered any problems in the womb or after they were born. They should have been perfectly healthy.

This puzzling study, published last month, echoes many performed on mice, worms and plants in the past few years in the name of a relatively young branch of science called epigenetics. In seeking to answer that eternal question of nature versus nurture – does our upbringing shape us or do our genes? – this field has radically introduced a mysterious third element into the mix: the life experience of previous generations.

There are many definitions of epigenetics, but simply put, says Professor Marcus Pembrey, a geneticist at University College London and the University of Bristol, it is a change in our genetic activity without changing our genetic code. It is a process that happens throughout our lives and is normal to development. Chemical tags get attached to our genetic code, like bookmarks in the pages of a book, signalling to our bodies which genes to ignore and which to use.

For decades, we have thought of our offspring as blank slates. Now, epigeneticists are asking whether in fact our environment, from smoking and diet to pollution and war, can leave “epigenetic marks” on our DNA that could get passed on to subsequent generations. They call the phenomenon epigenetic inheritance.

Until recently, most scientists assumed that whatever epigenetic marks we accrued during our lives were erased in our children. Embryos are known to be reprogrammed in the womb. “For something to be transmitted epigenetically from one generation to the next, it would have to resist this reprogramming,” says Professor Anne Ferguson-Smith, a geneticist at the University of Cambridge who ran the pregnant mouse study with her colleagues in Boston.

The notion that babies may retain some parental baggage has enormous repercussions for child development and evolution. Parents could suddenly find themselves responsible for passing on not only their poor genes, but also their poor lifestyles. And instead of adapting to our environments slowly over many generations, we may be doing it much, much faster. Some have even breathlessly suggested that Charles Darwin’s theories will need to be rewritten.

Before you throw out your biology textbooks, however, Ferguson-Smith warns that transgenerational epigenetic experiments are difficult to perform and can be misinterpreted. “Journals are very excited about this. They want to publish this stuff. But we must be more cautious,” she says. The basic problem is that researchers, including herself, still don’t understand the scientific mechanism behind epigenetic inheritance, which would explain exactly how it happens.

Professor Azim Surani, a leading developmental biologist and geneticist at the University of Cambridge, adds that while there is good evidence that epigenetic inheritance happens in plants and worms, mammals have very different biology. Surani’s lab carried out thorough studies on how epigenetic information was erased in developing mouse embryos and found that “surprisingly little gets through” the reprogramming process.

Professor Timothy Bestor, a geneticist at Columbia University in New York, is far more damning, claiming that the entire field has been grossly overhyped. “It’s an extremely fashionable topic right now. It’s very easy to get studies on transgenerational epigenetic inheritance published,” he says, adding that all this excitement has lowered critical standards.

Although many epigeneticists insist that they are slowly building up solid evidence in mice, when it comes to humans, the case is even more unclear. Among the very few sources of data are long-term medical studies over multiple generations. One that is often quoted tracked families following the Dutch famine of 1944, showing that starvation in one generation had health repercussions on grandchildren.

More recently, Pembrey, who has spent the last 15 years looking for proof of epigenetic inheritance in people, mined the Avon Longitudinal Study, which has monitored 14,000 new mothers and their children since the early 1990s. Pembrey and his colleagues found that men who had started smoking before they were 11 had sons who were more likely to be obese by the time they were teenagers. Meanwhile, the grandsons of grandmothers who smoked, even if their mothers didn’t, were bigger.

Some epidemiologists have questioned these correlations, but Pembrey is convinced that epigenetic inheritance is well placed to explain his observations. “The remarkable thing is, whatever study we’ve planned so far, we have seen results,” he adds. “This is a phenomenon.”…read more.

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