Richard C. Francis' Epigenetics: How a new field has changed the way we think about genes.

Reading between the lines.
June 20 2011 9:52 AM

Goodbye, Genetic Blueprint

What the new field of epigenetics reveals about how DNA really works.

Richard C. Francis. Click image to expand.

There are almost as many metaphors for genes as there are genes. One of the most familiar, and the hardest to let go of, is the tidy blueprint, at once reassuringly clear and oppressively deterministic: Our genome is the architectural plan for who we are. It tells our body how to build itself, setting our height, our health, and even our moods since before we are born. Small wonder that we imagine if we can read our genome, we will discover not just the truth of ourselves but perhaps our future, too. Remember the high hopes that spurred on the Human Genome Project in the 1990s? Though the genetic catalog is now largely complete, we still await many of the anticipated insights, and in Epigenetics: The Ultimate Mystery of Inheritance, Richard Francis, a writer with a biology Ph.D., traces the emergence of a different genetic paradigm. Our DNA shapes who we are, Francis reports from the research forefront, but it is far from a static plan or an inflexible oracle; DNA gets shaped, too. For good or ill, the forces that determine our fate can't be captured by anything so neat as a blueprint.

Francis's primer introduces a new field, whose roots predate the rise of pure genetic determinism. How is DNA itself shaped? The search for answers begins in the late-19th-century work of scientists such as Hans Driesch, whose study of sea urchin embryos revealed that the cell plays a key administrative role in an organism's development. He discovered that if you take cells from one location in the embryo—the area that will become, say, the spines--and plant them in another—the mouth area--their function changes: You don't get spines growing out of the mouth, you get a normal mouth. A cell's identity doesn't arise from a preordained genetic recipe inside it. Crucially, it is the cues that a cell gets from neighboring cells that affect how the genes inside it behave.

Epigenetics has taken its cue from this process, and sets out to explore not just how cells control the genes inside them but also how altered genes are passed on when cells reproduce—both within an organism's lifetime and, more fantastically, across generations. If you detect another historical antecedent, you're right. Looming over this new field is the once-derided Lamarck, who proposed in the 18th century that if a giraffe, for example, consistently stretches its neck to reach leaves, its children will be born with longer necks. Lamarck's ideas about how traits are acquired and passed down were mostly wrong. But the basic notion that an event in a parent's life can sculpt fundamental traits in a child, once consigned to the dustbin of biology, has been revived. The epigenetic quest is to discover how chemical attachments to genes shape the fate of an animal by altering the genes' long-term expression.

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If cellular regulation of genetic expression sounds complicated, it is, which is one reason—aside from our allegiance to the idea of some foreordained pattern to our lives—the epigenetic field has been slow to develop. The research that has been accumulating for decades upends the conception of "controller" genes that are either "on" or "off." Francis is a thorough guide to the many ways in which personality and health can play out through our genes but not be coded for in DNA. He proceeds step-by-step. After all, this is unsettling terrain: The notion of environmental forces that can be genetically determining does not fit our deeply etched nature vs. nurture categories. Francis begins by explaining what he calls "garden variety," or short term—rather than epigenetic—gene regulation, by way of androgens, like testosterone. This happens in normal development, but also in abnormal situations, such as when athletes abuse steroids. Where normal testosterone changes gene expression, extra testosterone causes a frantically altered gene expression, which leads to strong muscles, shrunken testes, and out-of-control aggression. The changes are direct. You take the steroids, they affect some of the cells in your body, the gene activity inside those cells changes, and then your body changes. The changes in garden-variety gene regulation end with the affected cells, and with you. When cells divide they do not pass along the abnormal genetic activation. The children of a steroid abuser inherit their parent's genes, but they do not inherit the synthetic steroid-induced changes to gene expression.

But gene expression doesn't change merely when you put chemicals in your body. The connections between people may shape it, too. In the 1990s, scientists began to explore how social status can influence biology. In one kind of African cichlid fish, for example, the males are either "territory-owning" tough guys who have vividly bright colors, huge testes, larger neurons, and lots of testosterone. Or they are nonterritorial and much less striking. The low-testosterone males do not get to breed. Scientists discovered they could manipulate the social status of fish, their testosterone level and all the hoopla that accompanies it, by changing only the fish's "friends." If they put big, territorial fish in a tank with much bigger, territorial males, the former-breeders lost color, their testes and neurons shrank, and they literally transformed into nondominant fish. When they put nonterritorial wallflowers in a tank with females and smaller males, they too were transformed, but in the other direction. As Francis points out, we obviously can't run this kind of experiment with humans. It nevertheless shows how context can change the way genes work.

Changes that arise from normal gene regulation happen in the short term, but epigenetic changes alter the way that genes react to the world for a very long time—even when the original cause has vanished. It is this rather shocking long-term influence that makes epigenetics one of most alluring—and terrifying—shifts in how we think about our genes. Epigenetic changes can occur in adulthood, in childhood, even in utero (a phenomenon explained in Origins by Annie Murphy Paul), with the consequence that an event you experienced as a child could dictate the ways your genes behave in a different situation as an adult. It may have been simple-minded to assume that we are programmed by our genes, but there was a weird egalitarianism in that: Even if we get different genes to begin with, we are under their sway in the same way. Epigenetic change means that not only do we start out as unwitting participants in a genetic lottery, but environmental forces we cannot see or control can mess with our genetic hardware and change our destiny. At the level of DNA, epigenetic change occurs when particular chemicals become attached to the gene, and stay there, altering how the gene behaves. The first of these attachments to be discovered, and still the best known, is from the methyl group. In 1980, it was shown that different degrees of methylation can alter gene expression in different ways. Demethylation can cause problems, too. Depending on the genes involved, one consequence can be unconstrained cell division, otherwise known as cancer.

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