The curious tale of epigenetics: How do genes change during our lives?

October 10th, 2023

Written by: Marissa Maroni

What if I told you that the two mice above are genetically identical (Figure 1)? All their genes match, and they are the same age. Yet somehow, one mouse is overweight with yellow fur, and one is smaller with brown fur. What could be making them so different? Surprisingly, the only difference is the diet of their mothers. The mothers’ diet, provided before and during pregnancy, made changes to their pups’ genes changing their coat color and likelihood of developing obesity.

Biologist often consider our genetic material, called genes, as defining who we are. These genes are passed down from a parent to a child and determine that child’s traits. These genes were once thought to be set in stone and not impacted by the experiences of the parent. For example, a parent that is a body builder isn’t going to give birth to a baby that’s jacked! But scientists have begun to change their mind on the belief that genes are set in stone. What if genes are only part of the story? And how could life experiences change genes?

How can genes change?

Everything that makes up who you are is stored in a genetic code, called DNA. Think of your DNA as an incredibly detailed manual about what you are. Every single cell in your body has this manual. However, every single cell does not necessarily need every part of the manual (a brain cell doesn’t need to know how to be a skin cell!). So, each cell in your body only reads the parts of the manual that it needs and ignores other parts by turning genes on and off as needed.

Genes can be turned on and off by items being added to the DNA sequence. Think of these items like adding a bookmark to your manual or highlighting a specific part. These changes are not permanent, can be reversed, and are known as epigenetic changes. These changes do not alter the sequence itself, so the manual is never re-written. However, different parts of the DNA can be read or ignored based on the epigenetic changes made to it. One way to “hide” parts of the manual is through the addition of a chemical group called methyl to the DNA sequence. Because of its chemical nature, methyl can be added to regions of the DNA to block certain genes from turning on (Figure 2)¹.

How can a mother’s diet can change a mouse pup’s coat color?

An interesting mouse breed can help us understand the impact of epigenetics on traits. This mouse breed normally has a dull brown, or agouti, fur color. However, sometimes these mice were both overweight and had yellow fur². When scientists looked at whether differences in the mouse’s DNA could explain the differences in fur color, they discovered that the yellow fur is due to a specific gene not being shut off. This could mean that the manual might have some highlight marks where it shouldn’t be! Suspecting that epigenetic changes could be responsible for the gene not being shut off the researchers looked at the amount of DNA methylation. They found that the amount of DNA methylation near the gene that isn’t shut off in yellow fur mice corresponded with coat color². The mice that had more DNA methylation, a mark that can shut genes off, were more likely to have brown fur.

The researchers, now clued into DNA methylation potentially being responsible for changes in fur color, wondered whether it could be added or subtracted to reverse the coat color change. Could pups inherit this epigenetic change to alter their fur? To test this, scientists asked whether feeding mothers different foods made them more likely to have yellow- or agouti-colored children. The experimenters gave pregnant mice either a regular diet or a supplemented diet with added nutrients that can provide the chemical methyl group needed for DNA methylation³. They found that mothers given the supplemented diet had far more agouti-colored mouse pups than yellow³. Further, these pups had more DNA methylation on the gene that is usually turned on in mice with yellow fur, suggesting that this gene is getting turned off by the methyl groups added to their diet³. Methylation added to diet can alter various regions of DNA ⁴ although, only regions around the gene turned on in yellow fur mice was measured for DNA methylation in this study.

Interestingly, maternal diet isn’t the only thing that can alter the coat color of mouse pups. Exposing pregnant mothers to environmental toxins can also alter fur color. Researchers found that the chemical toxin BPA, often found in plastics, led to more yellow coats⁵. Excitingly, providing the mothers with the supplemented diet could reverse this coat color change⁵. This exemplifies the power of epigenetic changes where genetics only partially explains the trait of an animal.

What could this mean in the brain?

Epigenetics can change a lot more than just the color of your hair. Researchers have found that events like early life stress can alter the epigenetic marks on your genes and are thought to cause changes in behavior and risk for developing disease⁶. For example, researchers found that babies born during the Dutch famine were more likely to develop diseases, such as cardiovascular disease and schizophrenia⁷. Although not directly tied to this increased risk, they found altered DNA methylation in these individuals⁸. Some researchers even hope that epigenetic changes can help explain why some people are more likely to develop Alzheimer’s Disease than others.  Building an understanding of these epigenetic changes can help determine potentially harmful genes that could contribute to diseases like Alzheimer’s disease and work on finding ways to reverse these changes.

References

1. Gibney, E. R., & Nolan, C. M. (2010). Epigenetics and gene expression. Heredity, 105(1), 4-13.
2. Dolinoy, D. C. (2008). The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutrition reviews, 66(suppl_1), S7-S11.
3. Waterland, R. A., & Jirtle, R. L. (2003). Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Molecular and cellular biology, 23(15), 5293-5300.
4. Maugeri, A., & Barchitta, M. (2020). How dietary factors affect DNA methylation: lesson from epidemiological studies. Medicina, 56(8), 374.
5. Dolinoy, D. C., Huang, D., & Jirtle, R. L. (2007). Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proceedings of the National Academy of Sciences, 104(32), 13056-13061.
6. Vaiserman, A. M. (2015). Epigenetic programming by early‐life stress: Evidence from human populations. Developmental Dynamics, 244(3), 254-265.
7. Roseboom, T. J. (2019). Epidemiological evidence for the developmental origins of health and disease: effects of prenatal undernutrition in humans. The Journal of endocrinology, 242(1), T135-T144.
8. Heijmans, B. T., Tobi, E. W., Stein, A. D., Putter, H., Blauw, G. J., Susser, E. S., … & Lumey, L. H. (2008). Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proceedings of the National Academy of Sciences, 105(44), 17046-17049.

Cover photo by Graphics@ HandiHow from Pixabay

Figures 1 and 2 made by Marissa Maroni in BioRender.com.