Though there are several ways these structural changes can happen, the best known—and the focus of most epigenetic research—is DNA methylation, which occurs when a small chemical compound called a methyl group attaches to a cytosine, one of the four nucleotides in the DNA code. Methylation turns off nearby genes in two ways: by blocking transcription factors from attaching to the gene (and thus keeping those factors from translating the gene’s code into a protein) and by altering the configuration of the DNA itself to make the gene less physically available for transcription. (In addition, some recent studies have suggested that methylation may sometimes alter the configuration to turn genes on.) When a cell divides and copies its DNA, it also copies the methyl group, so the same genes remain shut down in the replicated cells.

As an organism develops from a single cell into its final form, epigenetic mechanisms help cells become distinct tissues. So while every cell contains the same DNA code, each type of tissue—hair, heart, brain—differentiates itself through a unique combination of gene expressions. Epigenetic mechanisms turn off the genes that aren’t needed for a particular tissue type and help determine which proteins are expressed.

In recent years research has hinted that epigenetic mechanisms may be responsible for much more than just normal development. Development is inherently plastic, with organisms able to take a number of different paths depending upon the environment into which a fetus was introduced. But once certain developmental decisions are made, they are irreversible. David Barker, a professor of clinical epidemiology at the University of Southampton in England, has studied this idea in humans since the 1990s. In multiple studies he and others have found that babies with birth weights on the lower end of normal who grow up in affluent societies are much more likely to develop coronary heart disease, type 2 diabetes and hypertension as adults than are heavier babies. Barker has theorized that smaller babies are prepared for a diet low in carbohydrates and fat, and when they encounter just the opposite in the real world, they are predisposed to metabolic illnesses.

To see a mismatch between a baby’s real and predicted environment, consider the Dutch famine of 1944–45 and its legacy. When German forces cut off food supplies to parts of the Netherlands for six months, expectant mothers who starved during the final trimester were more likely to have babies who later developed type 2 diabetes. Programmed to expect hard times, these children grew up in an improving postwar environment. Researchers think epigenetic changes might have occurred in genes that regulate sugar absorption and metabolism. Other studies have linked a baby’s environment to kidney problems, asthma, osteoporosis and mental illness as an adult.

All these studies are merely correlational, with researchers noting that certain populations, having undergone a particular environmental stress early in life, have sometimes fallen ill years later. That raises questions of exactly how this may occur, whether epigenetics is the true mechanism and if there is anything to be done about it. While that has yet to be answered conclusively in humans, animal studies may be pointing the way.

For the purposes of epigenetics research, the agouti mouse is particularly apt. Its fur color is determined by the level of methylation on a piece of DNA found near the agouti gene. As a result, genetically identical offspring may look completely different from one another. One mouse might be yellow (indicating little methylation), another brown (a lot of methylation) and a third mottled (some cells with methylated genes, some not).

Randy Jirtle, an epigenetics researcher at Duke University, was intrigued by those tendencies and wanted to know whether early environmental influences could change the mouse’s levels of methylation. In a 2003 experiment, he fed agouti mothers folic acid, vitamin B12, choline and betaine—all methyl supplementers—during pregnancy. This not only increased the babies’ DNA methylation near the agouti gene but also boosted the likelihood that they would be brown, establishing that changes in DNA methylation are the mechanism that connects a mother’s diet to her offspring’s gene expression.

Then, in a 2006 study, Jirtle fed the mothers genistein, a component of soy, and found that it too increased methylation, making the offspring more likely to be brown. Next, he tracked the offspring’s adult weight and found that they were less likely to be obese. That’s because the agouti gene also governs the part of the brain that affects satiation. “The big question is how something that happens early, as a result of benign environmental influences, is linked to susceptibility to common diseases 20 or 30 years later,” says Jirtle. “At least for the agouti mouse, that link is DNA methylation.”