The Developing Genome: How Context Influences Genetic Architecture and Activity
"The understanding that genes can behave differently in different contexts undermines
[genetic determinism] in a significant way, and an important implication is that what we do matters,
and that the environments we occupy profoundly influence how we end up."
Dr. David Moore
Learn more about Dr. Moore: Books The Dependent Gene: The Fallacy of Nature Versus Nurture The Developing Genome: An Introduction to Behavioral Epigenetics Research http://pzacad.pitzer.edu/~dmoore/ Claremont Infant Study Center, BabyLab http://pzacad.pitzer.edu/~dmoore/babylab/ "I think in biology, things have changed a lot. Biologists are more open now to the idea that genomes are responsive, that DNA doesn’t do anything independently of its context."
"[N]ow we understand that the erasure is not complete and there are some cases where germ line effects do get transmitted."
[T]he genes we’re taught about in high school when we learn that a person with one ‘big B’ gene and one ‘little b’ gene will wind up with brown eyes—these kind of genes don’t actually exist in our DNA." "The steroid hormone cortisol and its receptors play a role in why the licking and grooming of Meaney’s rat pups led them to be less stressed in later development."
"Having said that, it is certainly the case that tweaking the epigenetic marks in a sperm or egg can potentially produce effects that will be transmitted across multiple generations."
"The understanding that genes can behave differently in different contexts undermines that idea in a significant way, and an important implication is that what we do matters, and that the environments we occupy profoundly influence how we end up."
|
David S. Moore, PhD, is a professor in the Psychology Field Group at Pitzer College, and director of the Claremont Infant Study Center. In 2001, he published the groundbreaking book, “The Dependent Gene,” arguing against the dominant paradigm of genetic determinism and for an understanding of development and biology that accounts for environmental and cellular context in how genes are expressed and ultimately in how traits develop.
His new book, “The Developing Genome,” (2015 Oxford University Press) expands on those themes by incorporating the explosion of research in developmental science in the past 15 years, with an emphasis on behavioral epigenetics. Interviewed by Jill Escher, March 2015 
I thought your 2001 book, The Dependent Gene, was strikingly ahead of its time for arguing against genetic determinism, and laying out a more contextually driven view of development. You said things in that book that are still new to people today, almost 15 years later. How does your new book, The Developing Genome, add to the first?
The basic takeaway regarding context-sensitive trait development is the same. But in the years since I wrote the first book, a lot has changed. So rather than a second edition, I thought it would be better to shift the focus from a theoretical emphasis to a more molecularly grounded argument. So, my new book more explicitly addresses how genes and environment interact. The concepts considered in the book affect how we approach psychology and philosophy of biology, and even how we think about human nature. This information is extremely important and that’s why it’s captured my attention all these years. The book’s emphasis is on behavioral epigenetics. Can you explain what that means? Behavioral epigenetics is an emerging branch of biology and psychobiology, in the border between the behavioral sciences and the biological sciences. It looks at how it is that the things we do, the things we’re exposed to, and the things we experience get inside of us and influence how our genes function and shape our traits, including our behaviors. For most of the 20th century, scientists thought of the genome as something static that you receive from your parents when you’re conceived. But we now understand that the structure and function of your genome actually changes in response to exogenous signals, so just like a living organism, DNA itself effectively develops over time. How do you think the mindset regarding these ideas has changed over these past 15 years? I think that depends on which corner of the world you’re looking at. In the mind of the general public, I don’t think much has changed. The public still seems to be very much enamored with the idea that genes are calling the shots and that your future is in some ways written in those genes. But I think in biology, things have changed a lot. Biologists are more open now to the idea that genomes are responsive, that DNA doesn’t do anything independently of its context. I think there’s widespread agreement now that epigenetics is interesting and important and real. There continues to be controversy about the extent to which epigenetic effects induced in one generation can be transmitted across generations to unexposed descendants, but this controversy shouldn’t diminish the insight that DNA does different things in different contexts. Though biology is moving forward, the field of psychology is still relatively in the dark about these ideas, as are most people who don’t study biology. One reason I think the developmental systems perspective hasn’t sunk in for much of the general public is because it’s very complicated. Many people like simplicity. They want to believe that there is a gene for each of our traits. Once you start telling such people about the true complexity of it all, they zone out because it can be hard to understand. Similarly, there’s a reason why people tend to ignore epigenetic effects in the germline: for a long time biologists were convinced that the epigenome was erased between generations. Of course, erasure is important to restoring totipotency to the gamete DNA, but now we understand that the erasure is not complete and there are some cases where germ line effects do get transmitted. Can you give an example of non-genetic but heritable trait development? One example can be seen in some famous pup-licking experiments by Michael Meaney and his colleagues at McGill University. When mother rats licked and groomed their pups a lot, those pups grew up to be less reactive to mild stressors because of an epigenetic change in some of their brain cells. In addition, female pups that were licked and groomed a lot grew up to be mothers that licked and groomed their pups a lot. This appears to be one way in which an early experience can have long-term effects on an animal. Importantly, these effects can then be transmitted to the next generation; in Meaney’s studies, the offspring wound up with the same epigenetic marks that their mothers had. And this transmission effect was caused by a behavioral intervention. A powerful and critically important idea presented in your book is something few people know: there is no agreed-upon definition of “gene.” Can you elaborate on that? Despite all the references to ‘genes’ that we hear in the mass media, biologists know there are actually several different meanings of that word, and that different scientists mean different things when they talk about genes. The “genes” scientists studied in the early 20th century—for example, the genes we’re taught about in high school when we learn that a person with one ‘big B’ gene and one ‘little b’ gene will wind up with brown eyes—these kind of genes don’t actually exist in our DNA. In fact, eye color is influenced by multiple DNA segments. At one time, scientists thought of genes as being located in specific places in the genome, but later they decided they’re more like computer programmers’ ‘subroutines.’ Contemporary theorists have rejected all of these ideas. Still, in various contexts, modern researchers continue to talk about genes in all of these various ways. The bottom line is that even though we hear talk about “genes” almost constantly these days, the fact remains that molecular biologists have not managed to agree on what a “gene” even is. You mentioned stress, which is a hormone-mediated state. I’m very interested in the effects of hormones, particularly steroid hormones, on the epigenomic marking of genes. Can you talk about that? Steroid hormones are capable of diffusing across cell and nuclear membranes, and they are transcription factors. That is, they can hook up with DNA and cause DNA to start doing its thing, engaging in the transcription process. That’s why they have the powerful effects they do—they can turn our genes on. The steroid hormone cortisol and its receptors play a role in why the licking and grooming of Meaney’s rat pups led them to be less stressed in later development. Now I don’t personally do empirical research that looks at these kinds of molecular phenomena; my empirical research is on infant development, specifically the development of perception and cognition in babies. But I’ve spent a lot of time thinking about hormones and their effects, because some sex differences in cognition seem like they might be related to differences in steroid hormone exposure, and I’ve recently been studying one of these sex differences in my lab. This work began when I encountered claims I thought were unwarranted—that males and females were born with certain innate differences in cognition, specifically in mental rotation ability, a skill that involves imagining what a three-dimensional object would look like if it was rotated into a new position in space. I thought those claims were kind of silly, and that a good way to potentially attack the idea would be to try to test mental rotation in babies. I came up with a way to study this, and to my surprise, I discovered that the boys actually did better than the girls when they were five months old. I was stunned. And I have since done the study a couple of other times. The sex difference has not always replicated but it has replicated several times. I really think there’s something there. And it may relate to the effects of hormones on the development of sex differences. Through this kind of roundabout way, I have come to understand a little bit about how hormones have their effects on developing brains. Testosterone, for example, is a transcription factor that can turn certain genes on. We can see the powerful effects of male sex hormones by studying children with CAH—congenital adrenal hyperplasia—which is a condition that can result from exposure to high concentrations of male sex hormones in utero. Girls with CAH often exhibit preferences for the kinds of playmates, toys, and activities that are more typically preferred by boys. Switching gears a bit, most of the book focuses on epigenetic phenomena as they occur in somatic cells, but on page 170 it turns toward the germ cells, recognizing that exposures can directly affect germ cell DNA. You recognize that the egg that made you was created in your mother when she was a fetus in 1936, to which I want to say to you, Happy 79th Birthday! But seriously, biologically speaking, isn’t potential direct germline tweaking (say, by the nutrition or drugs your grandmother took while the Professor Moore proto-egg was synthesized) the basis for the multigenerational epigenetic inheritance that’s making such waves in science these days? We’re still very much in the early days of understanding these things, so I’d say at this point, there’s a lot more we don’t know than we do know. Having said that, it is certainly the case that tweaking the epigenetic marks in a sperm or egg can potentially produce effects that will be transmitted across multiple generations. But to the best of my knowledge, this needn’t occur only when eggs are being synthesized in a fetus; theoretically, it could also happen later on in a young woman whose eggs are mature. Likewise, a male’s sperm are not synthesized prior to puberty; so, such effects could probably result from events experienced at many time points during development. Regardless, there are two important things to keep in mind about this question. First, there appears to be some reliable evidence in rats of transgenerational epigenetic effects of exposure to a particular kind of pesticide. But the evidence for transgenerational epigenetic effects in human populations—whether we’re talking about effects of drug exposure or malnutrition—is still circumstantial at this point, even though it’s extremely interesting. Second, as I noted earlier, there is good reason to believe that epigenetic effects can be transmitted across multiple generations even without the germline being involved at all. Taken together, the evidence we have to date suggests that even if the transgenerational transmission of epigenetic marks is relatively rare (which it might or might not be), there can be little doubt that our experiences—including the nutritional contexts and drugs we’re exposed to--can alter the epigenetic marks in some of our cells, and that these effects can, in some cases, be passed down to subsequent generations. What are some other implications of the themes that you cite in your book—about realizing that our DNA has an environmental responsivity? I end my new book specifically trying to address that kind of question. What we’ve discovered in the last 15 years has helped us understand how it is that our experiences affect the functioning of our genes. And one very important implication of this discovery is that our genes don’t single-handedly dictate what sorts of characteristics we have. A lot of people continue to believe that some of our talents, diseases, and preferences are caused by our genes alone, and that therefore, these characteristics are essentially fated. The understanding that genes can behave differently in different contexts undermines that idea in a significant way, and an important implication is that what we do matters, and that the environments we occupy profoundly influence how we end up. However, because we still don’t understand most of the specific ways in which our experiences influence our epigenomes, at present the takeaway message continues to be eat right, avoid toxins, have good healthy relationships with people, love your children, try to stay calm. What about implications for evolution? Of course when I was in school, I was taught like everybody else that evolution is a factor of random mutation and natural selection. But that paradigm is changing because of this DNA responsivity question. Yes. I continue to think the gene-based view of evolution is shifting, because phenotypes are not strictly determined by genotypes. As long as our adaptive characteristics are not determined by genes alone, it simply cannot be the case that natural selection operates on genes alone. So, the gene-based view of evolution that many of us learned in school definitely requires revision. But it’s important to note that the essential elements of Darwin’s theory do not require revision; it’s just the 20th-century “Modern Synthesis” of Darwin’s ideas and Mendel’s ideas that needs re-working. When Darwin wrote his theory, he had no conception of modern genes. As far as he was concerned, he just knew that characteristics—phenotypes—can be transmitted from one generation to the next. He didn’t know how, but he understood that any adaptive phenotype that could be transmitted from an ancestor could potentially help a descendant survive. By the mid-20th century, the assumption was that genes alone could account for the transmission of adaptive characteristics, so the Modern Synthesis posited that natural selection operated on genes, and only genes. But we now understand that since phenotypes are built as genes interact with their environments, adaptive phenotypes must be inherited via the joint transmission of both genetic and contextual factors. This understanding fits in well with Darwin’s theory as he originally envisioned it, a theory in which what matters is the transmission of phenotypes, not just genes. And in such a theory, natural selection has to select more than just the genes; it has to select the gene-environment complexes responsible for adaptive traits. In this way, the genes parents transmit and the environments parents transmit can work together to produce in offspring the adaptive characteristics that allowed the parents to survive and reproduce. Do you have an example you might want to share regarding how experiences have changed human behavior in certain contexts? My favorite example is the evolution of the DNA that helps us digest milk products. It’s pretty clear that like other mammals, there was a time in our evolutionary history when people were able to digest milk as juveniles but not when they became adults. But there are cultures, mostly northern European, that started a dairying culture because they were lacking clean water, and also needed additional sources of nutrients. Because a lot of the adults in these communities weren’t able to digest milk products, they were not particularly helped by the availability of dairy products in their environments. In those rare cases of people who had the DNA that allowed them to digest the lactose in the milk products, they had a survival advantage. So the dairying that people started engaging in contributed to the evolution of this ability to digest milk in adulthood. The genetic ability to produce lactase? I would just question if these Europeans have the random mutation and they passed it on or if that mutation or expression was in some way encouraged by a kind of destabilization at a molecular level influenced by the context itself. The fact that our ancestors were able to digest milk products when they were juvenile was a big help, in that the human genome clearly already had the ability to produce lactase. I don’t know why it is that this ability would ordinarily be lost in adulthood as it is in most other mammals. But it seems reasonable to me to imagine, to speculate that there was some epigenetic process that, in our evolutionary past, turned that ability off once we reached adulthood, and that being in a context where milk was freely available changed that epigenetic state and made the ability available into adulthood. We are out of time, but I thank you for your thought-provoking work and book. I hope it is widely read, it certainly deserves to be! And thank you! Read More Expert Interviews |