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DNA referees

Scientists are just beginning to understand the effect lifestyle choices and other environmental factors have on altering gene behavior, a rapidly emerging field called epigenetics.

May 03, 2010|By Amber Dance, Special to the Los Angeles Times

Your life story depends upon a combination of the DNA you're stuck with plus your environment, including all the little choices and events that happen over that lifetime.

But in recent years, researchers have discovered that, while DNA lays out the options, many of those life experiences — the foods you eat, the stresses you endure, the toxins you're exposed to — physically affect the DNA and tell it more precisely what to do.

The cause: a kind of secondary code carried along with the DNA. Called the "epigenome," this code is a set of chemical marks, attached to genes, that act like DNA referees. They turn off some genes and let others do their thing. And although the epigenome is pretty stable, it can change — meaning lifestyle choices such as diet and drug use could have lasting effects on how the body works.

"The thing I love about epigenetics is that you have the potential to alter your destiny," says Randy Jirtle, who studies epigenetics at Duke University Medical Center in Durham, N.C.

Twins provide an example of how environment can affect the actions of our DNA. Identical twins have identical genes, but sometimes one twin has autism or cancer while the other remains healthy. Studies show that as twins age, their epigenomes become less and less alike, probably causing a lot of those differences in fate.

Another provocative study: In 2009, researchers at Duke University Medical Center published a study in the journal BMC Medicine on epigenetics and autism. They found that some children with autism had extra DNA referees turning off a gene needed to respond to oxytocin, a hormone important in social interaction. The study was small, including only 40 children, but it suggests that turning off that one gene could cause the social problems people with autism have.

Many pharmaceutical companies are exploring the potential of epigenome-altering medicines: There are already a few cancer drugs that turn off cancer-promoting genes or turn on cancer-fighting ones. But since altering the epigenome could have far-reaching, unintended consequences, many scientists are wary of drugs targeted at less life-threatening conditions.

In short, the study of epigenetics is "booming," says Dana Dolinoy, a toxicologist at the University of Michigan School of Public Health in Ann Arbor.

Pick and choose

The regular DNA genome carries the code for every recipe involved in making a human (or antelope, or philodendron or whatever) — it's like "The Joy of Cooking." But just as some chefs never crack, say, the veggies chapter, while they dog-ear every page on desserts, different parts of the body pick and choose the genes they need.

The epigenome is part of what tells different cells in the body which DNA recipes to read and which to ignore. The small chemicals that attach to the DNA may cover up or restrict access to genes that aren't needed and keep others wide open and readable.

Jirtle compares the system to a computer: The DNA is the hardware — set and unchanging — and the epigenome is the software that tells it when, where and how to work.

Epigenetics might be especially important for pregnant women and infants, because much of the epigenetic code is laid down early in development. Dolinoy speculates that the time before puberty might also be important, since the genome and epigenome are gearing up to launch new genetic programs.

The chemicals that make up epigenetic codes ultimately come from diet. Folic acid, for example, is needed to produce epigenetic molecules that turn off many unwanted genes. Broccoli and garlic are good sources of other types of chemical tags that are part of the epigenome.

In a classic experiment published in 2003 in the journal Molecular and Cellular Biology, Jirtle showed how diet can affect these DNA referees. He studied certain mice that can have either brown or yellow pups. He showed that when pregnant mice eat lots of folic acid and other vitamins, they have mostly lean, brown pups. If those mothers instead eat a diet without the epigenome-enhancing supplements, they have more fat, yellow pups, which are prone to diabetes.

The DNA of the pups is the same — but mom's diet determined how they used those genes.

Dolinoy used the same types of mice to examine how bisphenol A, a toxin common in hard plastics, affects the epigenome of unborn mice. In a 2007 paper in the Proceedings of the National Academy of Sciences, she reported that mice whose diet included bisphenol A produced more fat, yellow pups. But eating folic acid counteracted those negative effects.

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