Jenny Chen ’16 and Caleb Vogt
In a nation where McDonald’s and Chipotle abound, we are frequently reminded that our diet can directly affect our personal health and wellbeing. But beyond changing our waistlines, can the foods we eat change the DNA in each of our cells? If so, can food also affect the health of our children, or perhaps even our grandchildren? The burgeoning field of epigenetics, which studies how the environment affects DNA, suggests that this may be the case. Epigenetic research is raising fascinating questions on how the dietary choices of our parents and grandparents may have direct effects on our own biology and behavior.
How does diet actually affect our DNA? A variety of food groups contain important nutrients such as Vitamin B12, Vitamin B6, folic acid, and methionine. Many of these nutrients contain molecules called methyl groups. As food is digested and processed, specific biochemical pathways strip these nutrients of their methyl groups and add them to the DNA, which aid in silencing or expressing genes. Foods such as brazil nuts, sesame seeds, leafy vegetables, broccoli, beef, chicken, and other meats, all contain nutrients that play a role in modifying the methylation status of genes and DNA6. We know that in order to be healthy, we require a balanced diet that contains the vitamins and minerals necessary for our cells to function. However, how those critical nutrients affect our DNA has largely remained a mystery until quite recently.
Some of the early investigations into how food can affect epigenetics came from observations of the diets of honeybees. Scientists have known for many years that the female larvae of honeybees are born as genetically identical sisters. However, just one of these sisters develops into the new queen of the hive, while the others develop into worker bees. Queen honeybees show vastly different body types and behaviors from worker bees. Worker bees are sterile while the queen bee produces all of the larvae in the hive. The queen will also kill rival queens and make distinctive communication noises known as “piping”, behaviors not typical of worker bees. These differences between genetically identical bees appear to be a direct result of their diet. Honeybee eggs are placed in individual cells of the honeycomb, where they stay until they grow into adult bees. As the honeybee larvae develop in their cell, adult worker bees choose one or two of the larvae to be exclusively fed a highly nutritional diet composed of “royal jelly” while the other larvae are fed a less nutritious diet. Scientists and beekeepers realized that the larvae fed the royal jelly consistently became the new queens of the hive, and that the queen bees are fed this royal jelly for the rest of their adult and reproductive lives.
Scientists discovered that they could mimic the effect of feeding larvae the royal jelly by knocking out a gene encoding the protein Dnmt3, which adds methyl groups to many genes in the DNA. Methylation of the DNA strand causes the DNA to become tightly wound around histone proteins, which help keep the extremely long DNA strand (almost 2 meters!) tightly wound inside the nucleus of cells, similar to a ball of yarn. This tight association between the DNA and the histone proteins blocks genes from being expressed, preventing them from carrying out their normal function. By functionally blocking the ability of Dnmt3 to donate methyl groups to the DNA, scientists were able to make larvae turn into queen bees even without the royal jelly diet (Kucharski et al., 2008). Additional research to determine the “secret ingredient” of the royal jelly revealed that the queenly cuisine contained high levels of a substance called phenyl butyrate. This compound prevents deacetylation from occurring, another epigenetic modification which typically represses gene expression. Since queen bees are continuously fed royal jelly throughout their lives, they express different genes from the other workers and maintain their seat on the honeycomb throne.
Epigenetic inheritance revolves around the idea that genetic information is carried in the structure of DNA as well as in the genetic code, and that this information can be transmitted to the next generation. But how do changes in the epigenetic state of a cell get passed on to an infant? As many mothers know, pregnancy is a critical period for the development of the child. Accordingly, a child is exceptionally susceptible to epigenetic changes as a result of the environment of the womb. Every mammal on the planet possesses a copy of the agouti gene locus which, under normal circumstances, is completely methylated. Normal mice with a methylated agouti gene generally have brown fur and have low risk of disease. Conversely, mice with an unmethylated agouti gene have yellow fur, become morbidly obese, and have much higher risk for disease. However, these mice are genetically identical. Evidently, the methylation state of the agouti gene alone can affect its expression in the mouse, despite no differences in the DNA sequence5.
Bisphenol-A (BPA) is a compound that, until recently, was commonly used in plastic water bottles and packaging material. After studies came out linking BPA to disruption of the endocrine system, a public health campaign centered around its potential negative health effects sounded the alarm and forced many companies to remove BPA from their products. However, while it is known that BPA affects the endocrine system, it also appears to exhibit epigenetic effects. In the lab, BPA has been shown to reduce methylation in the agouti gene. Introducing BPA into the diets of normal female mice more than doubled the amount of offspring expressing the agouti phenotype (i.e. overweight with yellow fur). When mother mice were fed diets containing both BPA and methyl-rich nutrients such as folic acid and genistein, which is found in soy, the effect of BPA is negated and the offspring appear normal like their mother. These studies were some of the first to clearly demonstrate that the mother’s diet during pregnancy can have an important impact on the epigenetics and health of their offspring (Dolinoy, Huang, and Jirtle, 2007).
Interestingly, the effects of diet on offspring may not only have to occur during pregnancy. A recent study found a clever way to show that high fat diets can change an animal’s sperm or eggs directly. Scientists started by feeding mice an extremely high fat diet; predictably, these mice became obese and developed diabetes. Then the scientists isolated both sperm and eggs from these unhealthy mice, and implanted them into healthy surrogate mothers which were fed a normal diet. The offspring had significantly higher risks for becoming obese and developing diabetes, despite the fact that they developed in the uterus of a perfectly normal mouse (Huypens et al., 2016). This finding suggests that mammals are capable of inheriting risk for diabetes and obesity from their parents, regardless of the diet they were fed during pregnancy.
If your parents diet can have effects on your epigenetics, can your grandparents diet have similar effects as well? Theoretically, this could occur in two ways. If the grandparent is pregnant, then chemical changes could affect the fetus’s developing gametes, which would then result in changes to the grandchild. This is known as multigenerational inheritance. Alternatively, an epigenetic change that directly modifies the gametes could theoretically be passed on down through the generations indefinitely, known as intergenerational inheritance. In a study of survivors of a Swedish famine, individuals who were between 9-12 years old during the famine tended to have grandchildren with relatively longer lifespans. Surprisingly, the reverse turned out to be true as well – food abundance during adolescence was correlated with a shorter lifespan4. While the actual epigenetic marks in these humans were not studied, similar studies have been carried out in C. elegans, a roundworm often used in genetic studies. When genes encoding the components of a methylation regulatory complex are silenced in C. elegans, descendants for the next two generations exhibited longer lifespans. This form of inheritance occurs because two of the components of the regulatory complex, ASH-2 and RBR-2, act in the germline, which includes the sperm and eggs of that organism. By doing so, these two components modify genes that regulate lifespan. Although humans are unlikely to have the same lifespan-modulating mechanism, it is very probable that nutrition can epigenetically impart its effects across three generations2.
The fact that diet can exert its effects in multiple ways, whether it is through you, your parents, or your grandparents, has ramifications for areas outside of science. For instance, the consequences of famine may extend far beyond the suffering immediately during the famine; the future progeny of the survivors may carry marks of the famine with them for the rest of their lives. During the infamous Dutch Hunger Winter in the last few months of World War II, most inhabitants of the affected areas who were starved due to the Nazi embargo only consumed 400-800 calories a day, which is only about 25% of the recommended daily caloric intake1. Studies examining children born during this time showed that children who were conceived during the famine had decreased methylation, or increased expression, at the IGF2 gene, which is implicated in various cancers2 (Hejimans et al., 2008). Those conceived during this time also had methylation differences in other genes that have been shown to be important for an individual’s health7.
Although the field of nutritional epigenetics remains in its infancy, the impact of diet on an individual’s biology is evident and quite possibly understated. These molecular changes as a result of diet could be critical for understanding how animals interact with their environment and how evolution could be driven by the quality and quantity of available food resources. Similarly, as the obesity epidemic rages across Western society, we must consider how this public health crisis may affect future generations. The nascent field of nutritional epigenetics shows great promise in elucidating the origins of disease, the widening obesity epidemic in Western society, and the vast long-term effects of food and diet.
- Carey, N. (n.d.). Beyond DNA: Epigenetics. Retrieved February 21, 2016, from http://www.naturalhistorymag.com/features/142195/beyond-dna-epigenetics
- Greer, E. L., Maures, T. J., Hauswirth, A. G., Green, E. M., Leeman, D. S., Maro, G. S., . . . Brunet, A. (2010). Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. Nature, 466(7304), 383-387. Retrieved March 17, 2016.
- IGF2 gene. (n.d.). Retrieved March 18, 2016, from https://ghr.nlm.nih.gov/gene/IGF2
- Kaati, G., Bygren, L. O., Pembrey, M., & Sjöström, M. (2007). Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet European Journal of Human Genetics, 15(7), 784-790. Retrieved March 17, 2016.
- Morgan, H. D., Sutherland, H. G., Martin, D. I., & Whitelaw, E. (1999). Epigenetic inheritance at the agouti locus in the mouse. Nature, 23, 314-318. Retrieved March 18, 2016.
- Nutrition and the Epigenome. (n.d.). Retrieved March 18, 2016, from http://learn.genetics.utah.edu/content/epigenetics/nutrition/
- Tanner, B. S., & Hanganu-Bresch, C. (2013). The Role of Epigenetic Regulation in the Development of Obesity: A Comprehensive Review. Journal of Young Investigators, 25(4), 44-51. Retrieved February 24, 2016, from http://www.jyi.org/wp-content/uploads/The-role-of-epigenetic-regulation-in-the-development-of-obesity-A-comprehensive-review.pdf
- Genetic Science Learning Center (2014, June 22) Nutrition and the Epigenome. Learn.Genetics. Retrieved March 22, 2016, from http://learn.genetics.utah.edu/content/epigenetics/nutrition/