Tabitha M. Powledge

Behavioral Epigenetics: How Nurture Shapes Nature

Identical twins have the same genes. Yet as individuals, they can be quite unalike in behavior, in personality, in health, and even in appearance, and they tend to grow more different as they age. How can genes that seem to be identical produce such different effects? A big part of the answer, scientists now think, is epigenetics—how nurture shapes nature. Epigenetic mechanisms are molecular events that govern the way the environment regulates the genomes of organisms. Epigenetic processes lead to individual differences in appearance, physiology, cognition, and behavior—the group of traits known as the phenotype. Scientists are at the very earliest stages of investigating them. The goal is to pry open one of nature’s most challenging black boxes: explaining how life experiences are transmuted into persistent changes in body function and behavior. In its brief history, epigenetics research has concentrated mostly on the early development of organisms. One strain of these investigations is development of behavior, and this line of research now has its own name: Behavioral epigenetics refers to the study of how signals from the environment trigger molecular biological changes that modify what goes on in brain cells. Here, the term environment mechanisms of memory—changes driven by experience—in the adult nervous system. “It’s not just that development and behavioral memory are rough analogs of each other, but rather that they are molecular homologues of each other,” he says. The two most studied epigenetic processes— regulation of the structure of threedimensional DNA and its associated proteins, plus chemical adjustments to DNA through mechanisms like histone modification—are essential both in development and in long-term memory formation. “It’s as if evolution has been efficient in the set of molecular mechanisms that cells use to trigger persisting changes. It uses those mechanisms in development when it’s patterning the organism, when it’s turning an embryonic stem cell into a neuron or a liver cell,” he says. “Then in the adult nervous system it has coopted some of those same mechanisms to trigger experience-dependent, persisting change in the function of neurons in the nervous system.” Several studies have established that both DNA methylation and histone modifications are essential for learning and remembering. Some examples are based on fear conditioning, in which mice learn to show fear of a particular location where they have been subjected to electric shocks. encompasses pretty much everything that happens in every stage of life: social experience; nutrition; hormones; and toxicological exposures that occur prenatally, postnatally, and in adulthood. If research on epigenetics is in its infancy, research on behavioral epigenetics is in embryo. Despite its embryonic state, behavioral epigenetics is already a vast topic, rife with complexities that grow more intricate every day. Discoveries seem to lead not to illumination but to more questions, and we have space here to touch on barely a few. Yet behavioral epigenetics has been held out as promising to elucidate, and perhaps even solve, immense medical troubles, such as mental retardation, autism, schizophrenia, and neurodegenerative disorders, and even social challenges, such as aging, addiction, suicide, child abuse, and child neglect.

Unlocking the secrets of the brain

The iron rod not only did not kill Gage, at first it did not even seem to have hurt him much, except that it cost him an eye. He moved and talked without difficulty, his memory was fine, he could still work, and his intellect appeared unaltered. But the brain damage Gage suffered did work a Jekyll-to-Hyde transformation on his personality. He changed from a kindly, cheerful, sensible, and intelligent family man, efficient and popular at work, into a profane and eviltempered drinker, a pigheaded, willful, lazy, inconsiderate liar. Luckily for neuroscience, his physician recorded Gages personality changes, generating some of our earliest insights into how specialized functions are distributed in various parts of the brain. And Gage continues to contribute to neurosciences growing body of knowledge. Scientists recently studied his skull using one of the many new methods and technologies for investigating the brain. Among the benefits of these technologies is that most of them are noninvasive-they pry open the black box of the brain, not with cranial

The inheritance of behavior in twinsResearchers find that no matter how genetically alike humans are, behaviorally they are not necessarily like peas in a pod

he future of research on human genetics, it is said, lies in molecular biology. Yet little of what we know, or think we know, about the genetics of human behavior emerges from DNA investigations, where the road to wisdom has proved decidedly rocky (BioScience 43: 362). Instead, behavioral genetics rests on a bedrock of statistical comparisons between groups of people, especially twins. Molecular biology will not supersede these biometrical studies anytime soon, although behavior geneticists expect eventually to combine the two. In the meantime, researchers who study twins are developing sophisticated approaches-some of which may even help molecular biologists solve their methodological problems and identify genes involved in behavior. And traditional twin studies have expanded their attention from mental illnesses, such as schizophrenia and the depressive disorders, to consider other behaviors. Recent twin studies have suggested a genetic basis for homosexuality, alcoholism in women, and even the risk of getting a divorce. Twins present a splendid natural experiment because they come in two varieties. Monozygotic twins (MZ or identical) result from the splitting of a single fertilized egg and are therefore genetic duplicates, sharing 100% of their genes. Dizygotic twins (DZ or fraternal) come from two eggs, each fertilized by a different sperm. DZ twins share, on average, only 50% of their genes, like any other pair of siblings. Therefore, a trait that turns up more often in both members of an MZ pair than it does in both members

The genetic fabric of human behaviorDo single genes or interacting genes determine the patterns of human actions

H uman behavioral genetics was for most of this century the most reviled and ridiculed branch of genetics research. In the past 20 years, sophisticated quantitative methods, along with more recent techniques for exploring DNA, have helped make behavioral genetics respectable at last. Despite its newfound acceptability, however, much about the biology of human behavior continues to elude analysis. Genetic explanations have, in the last 20 years, come to be the dominant paradigm in two major mental illnesses, schizophrenia and bipolar disorder. They also are more and more in vogue in studies of Alzheimers disease, the anxiety disorders, and autism. The largest study ever to show a major role for genes in male homosexuality was published in 1991, and a similar study on lesbians, reporting much the same results, appeared early this year. Genetics-based models are favored for funding at the National Institute on Alcohol Abuse and Alcoholism. Genetic research on human behavior is now so fashionable that even