Our Genetic Situation and the Situation of Our Genes
Posted by The Situationist Staff on August 29, 2009
For Observer, publisehd by the Association for Psychological Science, Eric Wargo wrote an excellent recap of the Presidential Symposium at this years APS Annual Convention in San Francisco. Here are some excerpts of Wargo’s article, titled “The New Genetics.”
Three Canadians . . . , Frances Champagne, (Columbia University), Michael Meaney (McGill University), and Marla Sokolowski (University of Toronto), spoke about their respective discoveries concerning (as Walter Mischel put it) “the gene by environment interactions that underlie what we become and how we differ.”
What Makes Us Unique?
A vast and growing amount of data shows that life experience can shape an individual’s development in amazingly subtle ways. Those influences can include nutrition and other environmental factors, as well as the amount of nurturance or stress experienced, especially early in life. The research of Champagne and her colleagues at Columbia shows that these influences involve actually facilitating or suppressing the expression of genetic information.
The metaphor Champagne uses is a library. A library contains many books, but they don’t do anything by themselves; in order to have an impact, to instruct and inspire, they have to be actually taken down from the shelves and read. The genome is the same way: Whatever information it contains, it has no effect on anything unless and until it gets transcribed (by messenger RNA) and translated into protein. “DNA, in order to be read, must be accessible; it must be unwrapped from the very condensed form in which it is stored in cells,” she explained.
Modifications such as the binding of methyl groups to the DNA (methylation) can affect how readily particular DNA sequences are read and, thereby, expressed. Changes in the cell environment influence methylation and, even more strikingly, these cellular changes are passed on to daughter cells. In other words, through epigenetic mechanisms — that is, functional changes in the genome that don’t actually involve altering the DNA sequence — nurture plays an active role in shaping nature’s expression, even from generation to generation.
In the case of Champagne’s research, it’s nurture literally: Specifically, how actively mouse mothers lick and groom their pups. Analogous maternal behaviors are common across mammals from mice to humans and are readily quantifiable in the lab. Champagne’s research shows that, via methylation, high versus low levels of licking and grooming influence the expression of a gene that governs estrogen receptors in a key brain area responsible for maternal behavior. In this way, the amount of nurturance received by a mouse pup influences that pup’s own maternal behavior later on — not merely as a matter of “learning,” but as a real change in the expression of key genes in specific cells.
“Changes to the epigenome,” she said, “are a cellular memory of an environmental event.” Such cellular memories are then passed on to offspring via behavioral and epigenetic modes of transmission. . . .
A Constant Dialogue
It is well known that the social environment in early life predicts the later health of organisms. The question is how. Champagne’s mentor Michael Meaney discussed the hormonal mechanisms by which life experiences like early stress become, as he put it, “embedded.”
“Development emerges as a constant dialogue between gene and environment,” Meaney said, “and in part that environment is social and economic. It is so for all species — it is social in that there is at least a maternal organism passing on signals to her offspring, and it is economic in that it involves at least nutrition, as well as potentially other signals.” Such signals have a long-term impact on gene expression, through cellular mechanisms of methylation and other processes.
Meaney’s work, like that of Champagne, looks at rodent maternal behavior — in this case, at its impact on later stress responsivity. The less licking and grooming infant rats receive, the more stress-reactive they are later. Offspring of more nurturant mothers are less easily stressed when they are adults than are offspring of less nurturant mothers. The same is true of offspring of less nurturant mothers raised by more nurturant foster mothers.
The hormonal mechanisms at work involve the body’s stress homeostat, the hypothalamic-pituitary-adrenal axis. The stress response system begins in the hippocampus, which initiates a domino effect of chemical signals that ultimately trigger the release of glucocorticoid stress hormones by the adrenal glands. It’s a self-regulating system, in that these glucocorticoids ordinarily act back on the hippocampus, telling it to release fewer of its signals. In other words, stress hormones normally limit themselves.
But the stress of low maternal nurturance — less licking and grooming — early in life can directly influence the cell environment in hippocampal cells, producing increased methylation of the gene controlling for expression of glucocorticoid receptors and thereby inhibiting those receptors’ expression. The result is that the hippocampus is less responsive to signals to tone down the stress response — and consequently, there is heightened stress sensitivity and all the health and behavior consequences that entails. These influences (as in the alterations of maternal behavior studied by Champagne) can be passed on across generations but can also be reversed either pharmacologically or through alterations in the environment.
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To read the entire article, including a summary of the eye-opening work of Marla Sokolowski, click here.