In part one of this entry I introduced epigenetics; in part two we focus on a more controversial specific form called transgenerational epigenetics.
Picture your parents having sex. No..no good, too weird? OK then, picture your grandparents having sex. Even weirder? Fine, picture your great-grandparents having sex. That one might not be as bad. Chances are you never met your great-grandparents, which makes them somewhat strangers to you. You had eight great-grandparents and though you might not even know their names, about 12.5 percent of your DNA was inherited from them. Now imagine your great-grandmother eating a ham sandwich while having sex with your great-grandfather. Could that ham sandwich somehow affect your great-grandmother’s DNA? Crazier still, could that ‘ham sandwich tainted DNA’ be passed down to the 12.5 percent that is now in you? No don’t be silly; of course a single ham sandwich does not influence your hereditary makeup. If, however, your great-grandparents ate a lot of ham sandwiches over the course of their lives, then that could influence your life. How could that be? We all learned in biology class that physical changes our ancestors go through have no effect on us. If your dad swung a hammer his whole life, that doesn’t mean you will inherit stronger arms. As we’ve learned epigenetics can affect how we respond to the environment. It was always assumed, however that these epigenetic changes were not passed onto our children. The epigenome becomes a clean slate during the development of eggs and sperm. This ensures that your one cell zygote Mr. Gadget Hat can develop properly. The only changes that you pass on to your kids are random DNA mutations in your egg/sperm cells acquire. Don’t tell that to the water flea Daphnia though.
These little gals can sense chemicals produced by predators when they are near and grow little protective helmets. As impressive as that is, what’s more impressive is that their offspring will also be born with those helmets and often this phenomenon even continues into their grandchildren.
The water flea helmet transformation is due to epigenetics. The Miami Dolphin helmet transformation is due to a dolphin with a helmet looking ridiculous.
There are multiple examples of transgenerational epigenetics in “lower” animals such as insects and even more examples in plants. Organisms such as these, however, have somewhat simpler developmental processes and are more amenable to change. Mammals, on the other hand such as humans, were not thought to be privy to this aspect of biology, but there is some controversial evidence that our sperm/eggs may not get completely wiped clean of epigenetic changes. A study in rats dealing with chemically induced infertility that persists into multiple generations is the strongest example of transgenerational epigenetics in mammals although it has come under scrutiny. But what about humans? What ever happened to your kinky ham sandwich loving great grandmother? The problem with humans is that they live too long relative to the average lifespan of human scientists. This makes it pretty hard to examine them across generations. But there has been a study that attempted to tackle transgenerational epigenetics in humans and it has gotten a lot of press lately.
A paper published in 2006 showed how the eating habits of grandparents influenced the life expectancy of their grandchildren. ‘Eating habits’, however, might be too weak of a phrase to describe the feast or famine conditions of the people used in the study. Överkalix is a remote area in Sweden comprised of small villages with a population of roughly 3700 people who are relatively genetically isolated. Some who live there can trace their Överkalix lineage back to the 1400s. This isolated community is highly dependent on their yearly harvest to sustain themselves and their livestock. A year with a weak harvest meant famine like conditions during the winter. The Överkalix people kept records on the quality of food harvests as well as birth and death records of family lineages, including how people died. This meticulous bookkeeping allowed researchers to make the following, somewhat convoluted, conclusion: Paternal grandfathers (your father’s father), who ate a lot between the ages of 9-12, had grandsons who lived shorter lives often due to diabetes. Conversely if paternal grandfathers had little to eat around the same age, their grandsons lived longer with less cardiovascular disease. The difference in lifespan was about 6 years, but after adjusting for socioeconomic factors the gap grew to 32 years. In other words, if your grandfather starved when he was a boy you would live, on average, 32 years longer. It sounds like a crazy notion, but this work has been highlighted on many pop culture and news outlets such as NPR’s radiolab, Discovery and PBS Nova.
Despite how relatively famous this work has become, the conclusions they draw seem to be very restrictive leading to two questions. 1. Why was this affect only seen between grandfathers and grandsons? And 2. What is special about the ages of 9-12? The authors argue that both of these specifications are further evidence that this phenomenon is due to epigenetics. The majority of traits you have, like how tall you are or your blood type, are a ‘blended cocktail’ of your parents’ genes. Some traits in genetics, however, are ‘sex-linked’ meaning you inherit them based on if you are a boy or a girl. If a trait is passed specifically down a paternal line then that suggests that it is sex linked to they Y chromosome. You’ve probably heard that girls have two X chromosomes (XX) while boys have an X and a Y (XY), but what does that really mean.
Picture your mother’s egg and your father’s sperm; I don’t care if it makes you uncomfortable, I’m not going through the whole grandparent, great-grandparent charade again. Your mother’s egg has half the amount of DNA necessary to make you, and your father’s sperm has the other half. This DNA is subdivided into 23 chromosomes, which are tightly bound DNA packages. The overwhelming majority of that DNA has nothing to do with whether or not you are a boy or a girl. One out of 23 of those chromosomes is called the sex chromosome. Your mom’s egg gave you a normal sized ‘X’ chromosome. Your fathers sperm, however, either gave you another normal sized X chromosome, if you are a girl; or, if you are a boy, it gave you a shriveled up little desiccated thing so small it could only make half of the letter X, which is called a Y. The default stage in human development is female. If your father’s sperm gave your mother’s egg another X, then your mother’s egg took one look at it and said, “I already got one of those, I don’t need two of them” and promptly turned one of them ‘off’. To become a man, however, requires something special, something unique, something extra-ordinary, something extraordinary, something like a manly tiny little Y chromosome. Your mom’s egg took one look at that Y chromosome and said, “Now there’s something I can work with!” and together the X & Y formed a boy.
So what does all this have to do with starving boys between the ages of 9-12 and their grandsons in Sweden? Well, if something is going to be passed specifically through the paternal side of a family then that would suggest that changes were made to the Y chromosome. Remember, the Y chromosome is small and has a relatively small number of genes. The majority of its genes play a role only in male development. The change in life expediency from the Överkalix study, however, was attributed to diabetes and cardiovascular disease. Could changes to the Y chromosome account for life expediency due to diabetes? Possibly, but the fact that the granddaughters of those starving grandfathers showed no statistical change in life expediency is puzzling.
Also, what’s so special about the ages of 9-12? The authors say that this is a pre-pubescent time called the ‘slow growth period’ of life during which the stem cells, which continually produce sperm cells, are maturing. The conclusion the authors made was that starvation affected the epigenome in those sperm stem cells. I have never heard of the ‘slow growth period’, but until recently I also didn’t know what a kumquat was, so my brain is not the best indicator of whether or not something exists. When you Google ‘kumquat’ you can get a ton of information on them from multiple sources. But when you Google ‘slow growth period’ you only get a handful of results ALL of which are in reference to the Överkalix study.
Left: Google image search for kumquat. Every picture is kumquat related. Right: Google image search for ‘slow growth period’. The first two images are directly from the Overkalix paper. The other images are mostly random economic figures.
In case it’s not evident, I have some doubts as to the validity of this study. Transgenerational epigenetics is a very new concept in biology. It represents a mechanism for explaining rapid evolutionary changes to our environment. Our bodies are constantly reacting to the world around us. It remains to be seen definitively if the lives we lead affect our future generations genetically, but for now epigenetics can serve as a cautionary tale about how we change the world around us. Because in the end, we may be changing ourselves too.
Anway, M. (2005). Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility Science, 308 (5727), 1466-1469 DOI: 10.1126/science.1108190
Pembrey, M., Bygren, L., Kaati, G., Edvinsson, S., Northstone, K., Sjöström, M., & Golding, J. (2005). Sex-specific, male-line transgenerational responses in humans European Journal of Human Genetics, 14 (2), 159-166 DOI: 10.1038/sj.ejhg.5201538
The Lab Hippo 