A new scientific study appearing in this week's issue of the journal Nature is challenging familiar ideas about genetic inheritance.

We can't change the genes we received from our parents. But our genes are controlled by a kind of instruction manual made up of billions of chemical markers on our DNA, and those instructions can be rewritten by our circumstances -- for instance, by obesity. According to the new research, they can even be passed along to children.

In a way it's saying the metabolic sins of the father can be visited on the daughters, even if the daughters haven't been conceived yet.

Andy Feinberg, professor of medicine and molecular biology, Johns Hopkins School of Medicine

The study was directed by Margaret Morris, an obesity researcher at the University of New South Wales in Sydney. Morris had previously explored the reasons why the children of obese mothers often become overweight themselves. But her attention shifted when a new graduate student from Malaysia arrived in her laboratory.

"She noted, in a clinic, that when a child arrived for weight management, usually both parents were obese, not just the mother," says Morris.

This wasn't too surprising. It makes sense that if a father is genetically predisposed to obesity, his daughter might be, too. But Morris wondered whether she might be seeing more than genes at work.

The Consequences Of Overeating

Morris set up an experiment with lab rats to see if the biological consequences of a father overeating could somehow get passed on to his daughters. "This is a study that I did for love," she says. "I didn't really have much funding for it. I had to crib money from all over to do it."

Morris took a group of genetically identical male rats, and put half of them on a high-fat diet. Predictably, those rats got fat and suffered symptoms of diabetes.

Then all the rats mated with normal females and had children. Morris looked specifically at the daughters. All of them had a similar genetic makeup, but those with overweight fathers had some of the same problems that their dads did. They weren't overweight, but their production of insulin was impaired.

This finding is fascinating, says Andy Feinberg, at the Johns Hopkins School of Medicine in Baltimore. "In a way it's saying the metabolic sins of the father can be visited on the daughters, even if the daughters haven't been conceived yet," he says.

The Grammar Of DNA

Feinberg thinks he knows how this may be happening. It's an example of an "epigenetic" effect, which is his specialty.

This field -- epigenetics -- is getting a lot of attention these days. It refers to things in and around our DNA, such as billions of chemical markers that attach to it. Those markers are signals that turn genes on and off. They tell the genes of a liver cell to behave differently from genes in a blood cell, for instance.

The sequence of our DNA -- the human genome -- has been called the book of life. Feinberg has his own metaphor for the billions of added signals that he studies. If the genetic sequence is the words of the book, the epigenome is the grammar, he says. "It helps to tell what the genes are actually supposed to do, and puts them in context."

Our genes don't change, or if they do, it's a rare and random event. But the grammar of the epigenome is changing all the time. It can also be disrupted by chemicals we eat or breathe.

Apparently it can also be disrupted by obesity, because Feinberg thinks those fat dad rats in Australia created sperm cells with a different pattern of epigenetic marks on their DNA; that's how the effect showed up in their children.

Michael Skinner at Washington State University in Pullman says epigenetic effects are swinging the pendulum of scientific attention from the genetic code back toward the impact of environment.

"I think that we're eventually going to have sort of a merger of this," he says. "I think that we're going to have an appreciation of the fact that there is an environmental influence on biology that probably through more epigenetic mechanisms. There's also a baseline genetic element of biology. And the two combined will actually give us more information about how things work."

Much of epigenetics is still a mystery. Scientists would like to know, for instance, how often epigenetic signals are passed on from parent to child, or even grandchild. So Morris, in Australia, is hoping to repeat her experiment and see if the effect persists over multiple generations.

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