Book Report: The Epigenetics Revolution by Nessa Carey Michael Ezem 11.24.2019 PCB4024.002 Epigenetics is the study of heritable changes in gene expression that do not involve changes to the DNA sequence, such as a change in phenotype without a change in genotype due to external factors which include but are not limited to environment (pollutants, stress), diet (lack of food or the right type of foods), and lifestyle (sedentarism, exercise). Epigenetics affects the quantity and quality in which the genes are switched on or off. The key to understanding the relationship between nature and nurture is epigenetics. “Epi-“ is Greek for above. Basically, small chemicals are added above the DNA or the proteins around the DNA that alter the expression of the DNA but do not affect the original DNA Sequence. If these chemical modifications are added or taken off during turning points in development they can have dire consequences for not only the rest of the life of that person but their kids and grandchildren who may never have come into contact with the stimulus that produced the epigenetic modification. To date, over 100 epigenetic modifications have been discovered such as methylation, histone acetylation, and ubiquitination. Methylation is the addition of methyl groups to the DNA bases (A, T, C, and/or G). Methylation affects how much a section of DNA is transcribed. The more a strand of DNA is methylated the less it is transcribed. There is a critical point in which the level of methylation results in DNA inactivation meaning that strand or section of DNA is not transcribed at all. So the proteins and genes from that section are neither active nor produced The purpose of DNA methylation is to maintain the correct levels of expression of the different cell types throughout the body. Defects in DNA methylation can lead to diseases or disorders like Rett’s syndrome. Clearly, DNA does not tell the whole story. The DNA functions as the blueprint or script that contains the genes that produce the proteins necessary to our survival. All cells have the same blueprint but interpret it in different ways along with varied molecular modifications. DNA does not carry out the thousands of functions required to keep us alive. The proteins do that. If the DNA sequence was all that mattered, then identical twins would be identical in every aspect. However, this is not the case. For example, when Manel Esteller perused the chromatin methylation and histone acetylation levels of newborn monozygotic twins there were nearly no differences. But when he reexamined the levels for these pairs of twins in their fifties, the DNA methylation and histone acetylation levels were substantially different. Genetically identical twins start out epigenetically similar but diverge as they get older due to exposure to different stimuli. These epigenetic modifications that occur over the twins’ lifetime are responsible for why one twin develops diseases such as schizophrenia or muscular dystrophy while the other does not. Twins can also be used to study the concordance rate or the degree to which genetics is the impetus for certain illnesses. With epigenetics we have been able to change our relationship with disease and injury. To elaborate, Shinya Yamanka was able to create immortal nonsenescent induced pluripotent embryonic stem cells (iPS) from cells already differentiated cells by inserting vectors containing high amounts of genes Oct4, ASox2, Klf4, and c-Myc. By being able to create an immortal stem cell line we no longer have to worry about running out of cells of any kind, especially those of the heart, brain, or blood cells. The effects of events that occur in one’s lifetime can last for multiple lifetimes. One example of this is the Dutch Hunger Winter that lasted from November 1944 to the Spring of 1945 in the Netherlands. During this time World War II was occurring. The Netherlands was still under German control. A German blockade significantly reduced the food available to the Dutch population. Thus, the babies born during this time profoundly affected. And later on in life, when these children gave birth their kids were also affected. Those four months of malnutrition affected three generations, over 70+ years. Mothers who were malnourished during the first 3 months of pregnancy gave birth to normal-weight babies who were acutely at risk of becoming obese. Mothers who were malnourished near or toward the end of their pregnancy gave birth to smaller babies who stayed minute for the rest of their lives struggling to gain weight and maintain healthy bone density. The kids born during the Winter and their children were affected by this event that they never even came into contact with. The Dutch Hunger Winter resulted in a famine that caused epigenetic changes to the Mother’s DNA that were transferred to their kids who passed it along to their kids. Unfortunately we still do not yet have the knowledge to reverse the effects of this tragic event, however by knowing what period your mother or grandmother gave birth to you, you can try to avail the effects. If predisposed to obesity eat smaller portions or vice versa. On a side note, well-known actress Audrey Hepburn’s, fragile bone structure and petite frame were due to this event. Although it only lasted four months of her life it affected for the rest of her life. Patently the answer is not nature or nurture but a combination of the two. Epigenetics the link between the two disciplines. It expounds why our biology, DNA and genetics act in certain ways; as well as why two people can have the same DNA sequence genotype, yet express two different phenotypes. Epigenetics can also help understand numerous diseases that have plagued humans for decades and reverse their detrimental effects. In addition, it can increase the vitality and the quality of life even into our later years and explains why organisms continue to be affected by epigenetic events long after they have occurred. This book serves as a foray into the discipline of epigenetics. I agree with the conclusions presented in this book. The information presented is backed up by numerous studies, experiments, and examples over seven decades. The most intriguing aspect of this book to me was the creation of new undifferentiated iPS cells that could be instructed to differentiate to cell of one's choice. This accomplishment will change the world forever because we now can replace cells that were once thought to be irreparable or replaceable like brain cells or heart cells. We can create replacement organs from this same process. No longer will people have to wait on organ donor lists, then take immunosuppressive drugs for the rest of their lives afterward, that allow them to live with their new healthy organ but an immunocompromised system that makes them susceptible to a variety of other illnesses and conditions. I would recommend this book to everyone because this information is vital for living. The study of epigenetics and the revolution occurring in this field is information one cannot live well without. The quality of one’s life and their future generations depends in part to a substantial degree of knowledge of epigenetics. The future may be gray, but it is blindingly bright with the advances of Shinya Yamanka and his IPS cells, Esteller and his twin studies, our deeper understanding of illnesses like Rett’s and Prader-Willi syndrome, Conrad Waddington who founded epigenetics and the epigenetic landscape and numerous others. We now have the knowledge to make better choices that not only affect our immediate lives beneficially but our grandchildren’s lives as well. We can begin to make better life choices as eating having a better diet that includes varied foods rich in carbohydrates, proteins, vitamins, minerals, and healthy fats. And also avoiding unnecessary stress and exercising regularly (at least three times a week) By carrying out these actions we can acquire and maintain the epigenetic modifications vital to our health while keeping the detrimental epigenetic modifications at bay. DNA does not tell the whole story. However, we have a better understanding of the picture with our knowledge of epigenetics.
