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Monster plants and our father's fears in new DNA research on epigenetics

Epigenetics suggests that our own life experiences or behaviour can affect the genes we pass on to our offspring

PUBLISHED : Sunday, 31 August, 2014, 1:22am
UPDATED : Sunday, 31 August, 2014, 1:22am
 

Until very recently, it seemed the overall picture of genetics was well known. DNA molecules encoded for a host of attributes that created organisms like you and me, and we essentially served as receptacles for our inherited DNA, perhaps passing them on via mixing with a sexual partner's DNA.

Darwinism ruled as the theory of evolution, and DNA was evidently the only way you could directly pass characteristics to your descendants. Ideas of naturalist Jean-Baptiste Lamarck, published in the early 19th century, had been derided and dismissed: there was no serious acceptance that changes a person makes, like a blacksmith developing powerful muscles, could be transmitted to their children.

Yet thanks to a recent flurry of research, there are indications that the true picture is more complex. This research is in a field called epigenetics, which concerns ways the DNA code is actually expressed and implemented.

Though reported findings and implications are intriguing, epigenetics is distinctly weird. Even its definition is fuzzy, and while there are strong signs epigenetic changes can be passed from one generation to another, no one can figure out just how this happens. This led to an article on the Nature website quoting William Kelly, a developmental geneticist at Emory University, in the US city of Atlanta, Georgia, who said: "Impossible things are happening every day." (Kelly was himself quoting a line from Rodgers and Hammerstein's Cinderella.)

During the 1740s, Swedish botanist Carl Linnaeus wrote of one of the apparently impossible things, after examining a specimen of common toadflax with remarkably different flowers. To him, it was a "monster", akin to a cow's calf being born with the head of a wolf. It was not until the 1990s that the mechanism for producing such a monster was discovered, as plant biologist Enrico Coen, in Norwich, Britain, found that a gene responsible for flower structure was switched off by chemicals known as methyl groups. Remarkably, too, this trait was passed through seeds to later generations.

A similar hereditary influence through an epigenetic alteration to a gene was reported in a study published last December. But this time, the gene belonged to mice, and resulted from a group of mice being sensitised to the smell of acetophenone. Firstly, when exposed to this smell, the mice were given a mild electric shock. Then, researchers assessed how anxious they became on hearing a loud noise, with and without the odour.

The next generation of mice also exhibited heightened sensitivity to acetophenone, even though they were spared shock treatment. DNA in the sperm of the smell-sensitised father mice had an altered pattern of methylation of the gene linked to sensing acetophenone.

Though the results seem real, what's known of genetic mechanisms suggest the effect is indeed impossible. Methyl groups should be stripped from DNA before sperm cells form, so how can the DNA subsequently have any memory of them?

Even so, other animal studies likewise indicate epigenetic changes can be passed from one generation to another. For instance, male mice with pre-diabetes fathered offspring with increased susceptibility to diabetes. Daughters of female rats that often lick their offspring in turn become nurturing mothers. But there are controversies, notably regarding a study that found pesticide and fungicide impacts on pregnant rats led to changes that persisted for at least four generations - results that have proven hard to replicate.

There are some doubts, too, regarding a study of people in Överkalix, an isolated municipality in northern Sweden. This found that if food was readily available for boys just before they reached puberty - perhaps leading to overeating - then their children and even grandchildren were at greater risk of cardiovascular disease mortality and diabetes. Though it seems this showed experiences leading to inherited traits, the study did not rule out other factors like the lifestyles of the children and grandchildren.

Another study of records from Överkalix found that men who had smoked before puberty were more likely to have sons with relatively high amounts of body fat.

Though to some researchers, epigenetics should refer to changes that can be passed from one generation to the next, the term is also used for influences that can occur within an individual's lifetime.

Cancer, for instance, appears to have links to abnormalities, with genes that should slow cell growth turned off, others that lead to faster cell growth switched on, leading to cells multiplying without control. This notion has led to a quest to find drug therapies that can alter - and perhaps reset - the epigenetic profiles of cancer cells.

There are indications, too, that behavioural changes in humans can have epigenetic impacts. Canadian psychologist Richard Tremblay has found that improving care for young boys in poor neighbourhoods reduced the likelihood they would become criminals in later life. He learned of the study involving nurturing mother rats, and initiated research with monkeys, finding differences in ways that DNA was expressed in those that were nurtured, and others that were separated from their mothers as infants.

Tantalisingly, Tremblay and colleagues have also found links between aggression in men and the way their DNA encoded for chemicals called cytokines. As yet, the results are based on a small sample size, and it is far from certain that the aggression is rooted in epigenetics: if the DNA encoding could be corrected, would this be enough to make the men behave better?

While you ponder the latter question, consider this: you may be able to make positive epigenetic changes, and do so today. In a paper published in July this year, researchers at Lund University, Sweden, reported changes within the fat cells of a group of slightly overweight, healthy men who began regular exercise. Over a six month period, the men shed fat and boosted endurance. But there were also changes to the ways methyl groups attached to DNA, including to genes already known to play some role in fat storage and risk of developing obesity or diabetes.

Lamarckians might be disappointed to note that such changes may not last long after exercise sessions, so seem unlikely to be passed on to children or grandchildren. But the results do show the benefits of exercise are far more than just skin deep.

Martin Williams is a Hong Kong-based writer specialising in conservation and the environment, with a PhD in physical chemistry from Cambridge University

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