DNA Is Not Destiny (Excerpted Article)

This is a fantastic article that documents that our DNA is not our destiny; that gene expression, for better or worse, occurs throughout our lives, in response to environmental stimuli and stressors, with profound effects on our health and the health of our offspring. Therefore, we can influence our health based on environmental exposures that are within our control, and our lifestyle choices.

(all emphasis/highlighting in the article is mine)

DNA Is Not Destiny Ethan Watters DISCOVER: published online November 22, 2006 Excerpt: for full article go to:

http://discovermagazine.com/2006/nov/cover

The new science of epigenetics rewrites the rules of disease, heredity, and identity.

Back in 2000, Randy Jirtle, a professor of radiation oncology at Duke University, and his postdoctoral student Robert Waterland designed a groundbreaking genetic experiment that was simplicity itself. They started with pairs of fat yellow mice known to scientists as agouti mice, so called because they carry a particular gene—the agouti gene—that in addition to making the rodents ravenous and yellow renders them prone to cancer and diabetes. Jirtle and Waterland set about to see if they could change the unfortunate genetic legacy of these little creatures.

Typically, when agouti mice breed, most of the offspring are identical to the parents: just as yellow, fat as pincushions, and susceptible to life-shortening disease. The parent mice in Jirtle and Waterland's experiment, however, produced a majority of offspring that looked altogether different. These young mice were slender and mousy brown. Moreover, they did not display their parents' susceptibility to cancer and diabetes and lived to a spry old age. The effects of the agouti gene had been virtually erased.

Remarkably, the researchers effected this transformation without altering a single letter of the mouse's DNA. Their approach instead was radically straightforward—they changed the moms' diet. Starting just before conception, Jirtle and Waterland fed a test group of mother mice a diet rich in methyl donors, small chemical clusters that can attach to a gene and turn it off. These molecules are common in the environment and are found in many foods, including onions, garlic, beets, and in the food supplements often given to pregnant women. After being consumed by the mothers, the methyl donors worked their way into the developing embryos' chromosomes and onto the critical agouti gene. The mothers passed along the agouti gene to their children intact, but thanks to their methyl-rich pregnancy diet, they had added to the gene a chemical switch that dimmed the gene's deleterious effects.

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With no more than a change in diet, laboratory agouti mice (left) were prompted to give birth to young (right) that differed markedly in appearance and disease susceptibility.

"It was a little eerie and a little scary to see how something as subtle as a nutritional change in the pregnant mother rat could have such a dramatic impact on the gene expression of the baby," Jirtle says. "The results showed how important epigenetic changes could be."

Our DNA—specifically the 25,000 genes identified by the Human Genome Project—is now widely regarded as the instruction book for the human body. But genes themselves need instructions for what to do, and where and when to do it. A human liver cell contains the same DNA as a brain cell, yet somehow it knows to code only those proteins needed for the functioning of the liver. Those instructions are found not in the letters of the DNA itself but on it, in an array of chemical markers and switches, known collectively as the epigenome, that lie along the length of the double helix. These epigenetic switches and markers in turn help switch on or off the expression of particular genes. Think of the epigenome as a complex software code, capable of inducing the DNA hardware to manufacture an impressive variety of proteins, cell types, and individuals.

In recent years, epigenetics researchers have made great strides in understanding the many molecular sequences and patterns that determine which genes can be turned on and off. Their work has made it increasingly clear that for all the popular attention devoted to genome-sequencing projects, the epigenome is just as critical as DNA to the healthy development of organisms, humans included. Jirtle and Waterland's experiment was a benchmark demonstration that the epigenome is sensitive to cues from the environment. More and more, researchers are finding that an extra bit of a vitamin, a brief exposure to a toxin, even an added dose of mothering can tweak the epigenome—and thereby alter the software of our genes—in ways that affect an individual's body and brain for life.

The even greater surprise is the recent discovery that epigenetic signals from the environment can be passed on from one generation to the next, sometimes for several generations, without changing a single gene sequence. It's well established, of course, that environmental effects like radiation, which alter the genetic sequences in a sex cell's DNA, can leave a mark on subsequent generations. Likewise, it's known that the environment in a mother's womb can alter the development of a fetus. What's eye-opening is a growing body of evidence suggesting that the epigenetic changes wrought by one's diet, behavior, or surroundings can work their way into the germ line and echo far into the future. Put simply, and as bizarre as it may sound, what you eat or smoke today could affect the health and behavior of your great-grandchildren.

All of these discoveries are shaking the modern biological and social certainties about genetics and identity. We commonly accept the notion that through our DNA we are destined to have particular body shapes, personalities, and diseases. Some scholars even contend that the genetic code predetermines intelligence and is the root cause of many social ills, including poverty, crime, and violence. "Gene as fate" has become conventional wisdom. Through the study of epigenetics, that notion at last may be proved outdated. Suddenly, for better or worse, we appear to have a measure of control over our genetic legacy.

"Epigenetics is proving we have some responsibility for the integrity of our genome," Jirtle says. "Before, genes predetermined outcomes. Now everything we do—everything we eat or smoke—can affect our gene expression and that of future generations. Epigenetics introduces the concept of free will into our idea of genetics."

Scientists are still coming to understand the many ways that epigenetic changes unfold at the biochemical level. One form of epigenetic change physically blocks access to the genes by altering what is called the histone code. The DNA in every cell is tightly wound around proteins known as histones and must be unwound to be transcribed. Alterations to this packaging cause certain genes to be more or less available to the cell's chemical machinery and so determine whether those genes are expressed or silenced. A second, well-understood form of epigenetic signaling, called DNA methylation, involves the addition of a methyl group—a carbon atom plus three hydrogen atoms—to particular bases in the DNA sequence. This interferes with the chemical signals that would put the gene into action and thus effectively silences the gene.

Until recently, the pattern of an individual's epigenome was thought to be firmly established during early fetal development. Although that is still seen as a critical period, scientists have lately discovered that the epigenome can change in response to the environment throughout an individual's lifetime.

........... In 1999 biologist Emma Whitelaw, now at the Queensland Institute of Medical Research in Australia, demonstrated that epigenetic marks could be passed from one generation of mammals to the next. (The phenomenon had already been demonstrated in plants and yeast.) Like Jirtle and Waterland in 2003, Whitelaw focused on the agouti gene in mice, but the implications of her experiment span the animal kingdoms.

"It changes the way we think about information transfer across generations," Whitelaw says. "The mind-set at the moment is that the information we inherit from our parents is in the form of DNA. Our experiment demonstrates that it's more than just DNA you inherit. In a sense that's obvious, because what we inherit from our parents are chromosomes, and chromosomes are only 50 percent DNA. The other 50 percent is made up of protein molecules, and these proteins carry the epigenetic marks and information."

....... Michael Meaney a biologist at McGill University and a frequent collaborator with Szyf, has pursued an equally provocative notion: that some epigenetic changes can be induced after birth, through a mother's physical behavior toward her newborn. For years, Meaney sought to explain some curious results he had observed involving the nurturing behavior of rats. Working with graduate student Ian Weaver, Meaney compared two types of mother rats: those that patiently licked their offspring after birth and those that neglected their newborns. The licked newborns grew up to be relatively brave and calm (for rats). The neglected newborns grew into the sort of rodents that nervously skitter into the darkest corner when placed in a new environment.

Traditionally, researchers might have offered an explanation on one side or the other of the nature-versus-nurture divide. Either the newborns inherited a genetic propensity to be skittish or brave (nature), or they were learning the behavior from their mothers (nurture). Meaney and Weaver's results didn't fall neatly into either camp. After analyzing the brain tissue of both licked and nonlicked rats, the researchers found distinct differences in the DNA methylation patterns in the hippocampus cells of each group. Remarkably, the mother's licking activity had the effect of removing dimmer switches on a gene that shapes stress receptors in the pup's growing brain. The well-licked rats had better-developed hippocampi and released less of the stress hormone cortisol, making them calmer when startled. In contrast, the neglected pups released much more cortisol, had less-developed hippocampi, and reacted nervously when startled or in new surroundings. Through a simple maternal behavior, these mother rats were literally shaping the brains of their offspring.

....Meaney says the link between nurturing and brain development is more than just a curious cause and effect. He suggests that making postnatal changes to an offspring's epigenome offers an adaptive advantage. Through such tweaking, mother rats have a last chance to mold their progeny to suit the environment they were born into. "These experiments emphasize the importance of context on the development of a creature," Meaney says. "They challenge the overriding theories of both biology and psychology. Rudimentary adaptive responses are not innate or passively emerging from the genome but are molded by the environment."

.....Through epigenetic alterations, our genomes retain something like a memory of the environmental signals received during the lifetimes of our parents, grandparents, great-grandparents, and perhaps even more distant ancestors. So far, the definitive studies have involved only rodents. But researchers are turning up evidence suggesting that epigenetic inheritance may be at work in humans as well.

....Michael Meaney, who studies the impact of nurturing, likewise wonders what the implications of epigenetics are for social policy. He notes that early child-parent bonding is made more difficult by the effects of poverty, dislocation, and social strife. Those factors can certainly affect the cognitive development of the children directly involved. Might they also affect the development of future generations through epigenetic signaling?

"These ideas are likely to have profound consequences when you start to talk about how the structure of society influences cognitive development," Meaney says. "We're beginning to draw cause-and-effect arrows between social and economic macrovariables down to the level of the child's brain. That connection is potentially quite powerful."