Epigenetics discoveries challenge outdated medical beliefs about DNA, inheritance and gene expression

In a study published in the May issue of Nature Reviews Genetics, Eric Richards, Ph.D. proposed that changes such as alternative DNA packaging and small chemical additions to DNA bases that prevent the expression can be passed on and should be considered soft inheritance.

Richards, professor of biology at Washington University in St. Louis, analyzed past studies of epigenetics -- a Greek term meaning "above and beyond the gene" -- and evolution, and found that there is evidence in both the plant and animal kingdoms that supports the notion of soft inheritance.

One of the mechanisms Richards points to is known as DNA methylation, or the chemical modification of the DNA chemical subunit cytosine. Studies have shown that a lack of proper DNA methylation can cause developmental problems in higher organisms, including stunted growth in plants and death in mice.

Richards has also studied epigentics' effect on DNA packaging, noting that DNA that is "loosely wrapped" around proteins is easier to access. This, along with the location of DNA within the nucleus, presents another factor that affects the regulation of gene expression.

Such theories, Richards said, tend to provoke a negative reaction from his peers who remain steeped in outmoded beliefs about DNA.

"Epigenetics as soft inheritance in mammals puts us on a slippery slope that many people don't want to visit," he said.

The reaction was similar for the theories of pre-Darwinian evolutionist Jean-Baptiste Lamarck, who believed that the environment plays an important role in organisms' acquisition of evolutionary characteristics. Shore birds, for example, acquired long legs by constantly trying to stretch their legs and lift themselves out of the water, Lamarck believed. But many of Lamarck's theories are now being shows to be surprisingly correct, decades later.

"When most biologists hear the name Lamarck or the term soft inheritance, the reaction is, 'Oh my God, here we go again,'" Richards said. "But from a molecular biology point of view there is a mechanism to do soft inheritance, and epigenetic inheritance can be construed as a form soft inheritance. That's all I'm saying."

"The really heretical thing to say is that the environment could be pushing the epigenetic information in a direction that is beneficial," he said. "This is the more extreme variation of soft inheritance that raises the hackles."

One such hackle-raising study observed the epigenetic changes in mice hybrids from diet in a field Richards refers to as "nutritional epigenomics." In the study, researchers attempted to affect the DNA methylation of pregnant mice through varying levels of folate and B vitamins.

"The idea was: If you pump these pregnant moms up with these dietary supplements, you might be able to skew the DNA methylation patterns, and thus skew the way the mice come out at the end of the day, and it works,'" Richards said. "In this particular instance that says what you're getting fed in the womb influences your phenotype; physical and physiological attributes."

"These findings are revolutionizing our understanding about the role of nutrition and other environmental factors in human health. What they are showing," added Mike Adams, a holistic nutritionist, "is that your health is certainly not controlled entirely by your genes. Nutrition, it turns out, affects the way your genetic code is expressed. As a result, nutrition and other environmental factors determine your health just as much as your genetic code."

According to a separate study, early grooming and nurturing of rat pups by their mothers affected the methylation of a glucocorticoid receptor gene, found in the hippocampus in the brain. This nurturing apparently activates the glucocorticoid receptor and provides the pups with an enhanced ability to handle stress later on in their lives. Richards said the process appears to be brought on by changes in DNA methylation through changes in DNA packaging.

"These studies do not demonstrate inheritance between generations, but they do show that the early nutritional environment in the mice and early behavioral environment in the rat studies can change the DNA packaging on the genome, and that that is 'remembered' in the cell divisions that make the rest of the organism, " Richards said. "But this is not from one generation to another. No one has shown that yet."

Richards said that more extreme variations of soft inheritance would require that it be proven, one way or another, whether environment can induce an inheritable epigenetic change in an organism.

"Certainly, nobody has shown that an epigenetically induced beneficial or adaptive change has been inherited," Richard admitted, but he pointed out that there was also no reason to discount the idea of epigenetic inheritance.

"The big questions to resolve are how many epigenetic changes are induced by the environment, what types of phenotypes result from these changes, and how many of these epigenetic changes are inherited," he said.

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