Saturday, April 12, 2014

Epigenetics: Are Nature and Nurture Really So Different?

Image from: http://robbiestudent.com/
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This semester, I am taking a class called "Biological Embedding of Social Factors." The premise of the class is that we have spent so many years arguing whether health conditions are the result of nature or nurture, without considering that our lived experiences (and those of our ancestors) can actually affect our biology! Sometimes nurture is nature and vice versa. Often, this debate takes place in the context of determining whether a disease is caused by genetic factors or environmental factors. Or if by both, how much is caused by one or the other? As I am learning in class, however, the study of genetics has not turned out to be the panacea it was originally thought to be, and many processes are more complicated than an either/or categorization of genetic versus environmental effects. Sometimes, we may have an identical gene or set of genes that does completely different things depending on context and experience!

Consider first the human body and its parts. Each part has the same set of genes as all other parts, but each part looks completely different from others. The cells in your skin have the exact same genetic makeup as the cells in your bone marrow, and yet one set of cells creates more skin and the other set produces blood cells. How do these two genetically identical cells do completely different things? In scientific terms, we say that the genes are being "expressed" differently in the two cells. Clearly, it is not just the genetic makeup of the cell that determines what the cell does. Something outside of the genome is interpreting what a particular gene means and then translating that into what they cell should do!

This is the type of question being studied by the field of epigenetics, which literally translates to "outside of genetics."

I am not going to get into all of the details of how these processes work (and many processes are still unknown), but rather, I just want to share a few particularly interesting findings to get your juices flowing about how the environment can actually affect outcomes that we often think of as being predetermined by genetics. I find it helpful to imagine a gene or set of genes that, rather than telling the body to "Make X happen," actually tell the body, "If you encounter situation A, make X happen, and if you encounter situation B, make Y happen."

Animals

One interesting example is that even though there are genes known to determine the coat color of  mice, the diet of pregnant mice can still affect the coat color of their offspring. Scientists are able purchase inbred mice strains in order to get genetically identical mice and then feed them different diets to isolate the effects of the dietary supplements. As it turns out, among mice who have the gene for yellow fur coats, mice fed a high-methyl diet are more likely to have gray offspring, whereas those not fed this diet tend to have yellow offspring. The methyl diet effectively "turns off" the yellow coat genes in the offspring! Interestingly enough, the yellow-coated mice are also known to experience increased risk of other health problems. (Wolff, Kodell, Moore, & Cooney, 1998;  Begley, 2009)

Another example that I found to be fascinating is that of the minute parasitic wasp. This wasp actually lays its eggs inside a host insect, either a butterfly or an alder. Wasps bread in butterflies develop wings, whereas wasps bread in alders do not develop wings. One might think that having wings or not having wings would be genetically determined, and in many ways, it is, because wasps have genes that allow them to develop wings in the right conditions. Yet the gene is able to be expressed in a completely different phenotype (visible outcome), depending on the growing conditions of the egg (Gottlieb, 1998)! We might infer that there is some sort of hormone, diet, or other chemical environment in the host insect that actually tells the genes for wings whether or not to be expressed.

Yet one more example is that of the water flea. Offspring are born with a "helmet" for protection if the mother has ever encountered a predator and no helmet if the mother has lived a care-free bug life (Begley, 2009).

There are many such examples of this phenomenon in nature, revealing that animals with identical genes can actually adapt, such that the genes remain the same, but get expressed very differently in response to environmental stimuli.

Humans

In the human realm, scientists are currently asking questions about whether traumatic or prolonged stress exposures (which are known to alter brain chemistry, hormone production, etc. for some individuals who experience them) may also affect the offspring of individuals who experience these exposures. There is already evidence that individuals who experience PTSD have lower levels of cortisol, and children born to these parents may also have lower levels of cortisol throughout their lives, without ever having been traumatized themselves (Yehuda, Halligan, Bierer, 2002). This in turn may make these offspring more susceptible to PTSD if they do encounter a trauma in later life and may also be passed down to their offspring.

Likewise, there is evidence that maternal stress exposure in utero, or even before conception, affects the brain development of offspring, and thus the ability of offspring to handle stress "appropriately" for the rest of their lives (Matter, 2014). While children almost certainly learn many stress coping techniques, either adaptive or maladaptive, from watching their parents and peers, the biological effects of parental stress before birth are of special epigenetic interest. It is not just that children learn from observation after being born, but also that during fetal development, the child's biological abilities to produce and regulate stress hormones, to interpret stressful experiences, to grow certain regions of the brain that control stress response, etc. are being formed. The mother's lived experience is reflected in her hormone levels and other biological traits, which may then affect the way that developmental genes are expressed in the fetus. This fetal development, in turn, informs the specific way the individual will be able to either learn or not learn from their surroundings after they are born. Although these developmental traits are not completely deterministic of behavior or future health outcomes, they can act as a major hurdle or point of susceptibility for those affected and thus make it more difficult for individuals and populations to achieve good mental and physical health.

On another topic, studies show that children of mothers who were pregnant with them during times of famine experience significantly higher rates of obesity, diabetes, and schizophrenia as adults (Lumey, Stein, & Susser, 2011). So while the underlying genes for how to develop a healthy digestive system or a healthy brain may not change due to famine, something about famine affects the way these genes get expressed in development. Similar questions are being asked about a variety of mental illnesses, heart disease, personality, sexual development, and many other human health outcomes for which human biology might be affected by exposure to violence, historical traumas (like slavery), pesticides, household chemicals, and many other experiences.

The question is no longer solely about whether genes predispose a person to a certain health outcome, but also about whether the experiences of our parents, grandparents, and even more distant ancestors are affecting the way our genes are being expressed.


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