Dr. Mir Anayat
A gene is the basic physical and functional unit of heredity which is transferred from a parent to offspring and is held to determine some characteristic of the offspring. The word “epigenetics” was introduced in modern science in 1942 by Conrad Hal Waddington, a British developmental biologist. As the Greek prefix “epi” means “upon, over, on top of”, the “epigenome” is thought to be an additional, secondary informational level on top of the genetic code. Epigenetics is the study of gene expression, which can be modified without change in gene sequence. These alterations in gene expression can be inherited and reversible.
Since epigenetic changes control almost every aspect of health and disease in man. It is speculated that some yet undiscovered link between will/mental status and epigenetics could be the cause behind events responsible for “faith cures” transgenerational behaviors and “placebo effect”.
The basic mechanism of epigenetic inheritance can be better explained after understanding the method in which DNA is packed inside a cell nucleus. The three major groups of changes which contribute to defining the epigenome of a cell: DNA methylation, histone modifications and RNA associated silencing. Histone and DNA modifications are highly dynamic, a property that is crucial for the regulation and control of cellular proliferation, differentiation and survival. Studies have shown that epigenetic modifications acquired in one generation may be transferable to subsequent generations. Studies in mice found that when one generation of mice were conditioned to fear the odor of acetophenone before conception, the subsequent two generations were shown to have an increased behavioral sensitivity towards acetophenone odor without any prior exposure to the same.
During pregnancy, environmental exposures can influence the development of the offspring and increase the risk for metabolic diseases, like obesity, later in life. One maternal factor that has consistently been shown to influence gene expression is maternal nutrition. A Dutch study has shown that, after world war II when people of Netherlands were to face food embargo for a long period of 5 months, the children born from famine effected pregnant ladies were having low birth weight and increase risk to obesity. Later it was also found in subsequent generations. These Studies have clearly shown that how maternal nutrition can influence offspring’s health.
Epigenetic Marks can be altered after birth – it was shown in a study that those rat pups whose mother licked them extensively and groomed well dealt the stress better as compared to those who ignored the rat pups. It was found that this behavior of mother rat allowed the glucocorticoid receptor gene to turn back on and it stays on in those pup’s brains throughout their lives.
Which factors influence Epigenome?
Besides genetic factors, studies reveal that environmental and nutritional factors also affect neuronal functions, probably via epigenetic mechanism:-
- Diet: Diets high in such methyl rich nutrients may significantly alter gene expression and offer protective health benefits.
- Social interaction and behavior: When mice were subjected to odor-fear conditioning prior to conception, increased behavioral sensitivity was observed in offspring in subsequent two generations.
- Exercise: Exercise has been shown to induce positive changes in DNA methylation within adipose tissue and regulate metabolism in both healthy and diseased individuals
- Pharmaceutical drugs: Pharmacoepigenetics is the study of inter-individual variations in epigenetic modifications as a result of prescribed pharmaceutical drug use.
- Drugs of abuse: Recreational drugs like cocaine also including opiates, amphetamines, alcohol and nicotine modify the epigenome by altering methylation patterns in areas such as the nucleus accumbens of the brain, the major pleasure reward center.
- Smoking: Smoking is a major trigger for carcinogenesis. It is likely that tobacco smoke exposure can alter the fetal epigenome.
- Alcohol: Alcohol induced neuro-adaptations like tolerance and dependence are a result of epigenetic modulation at the neurobiological level.
- Environmental chemicals: Encounters with pesticides, toxins and synthetic compounds can methylate genes in adults and also promulgate diseases decades later in offspring following in utero exposures.
Epigenetic mechanisms have been identified behind numerous diseases such as Cancer by deactivation of tumor suppressor genes . But advances in epigenetic technology may soon allow repair of defective epigenetic modifications by a variety of therapeutics. For example the drug azacitidine, the first FDA-approved epigenomic drug, treats leukemia by reactivating tumor suppressor genes and similar drugs are now in development. Other diseases such as Alzheimer’s Disease, Arthritis, Cardiovascular Disease and autoimmune diseases (Type 1 Diabetes, Systemic Lupus Erythematus ) have been shown to have an epigenetic basis.
Epigenetic studies over the past decade have contributed fascinating insight into the role of DNA methylation as a rich source for interactions between our environment and static genome. Further research using human study populations and animal models, especially those with clinical relevance, promises a greater understanding of the regulatory role of epigenetic processes in aspects of brain development to psychiatric disorders. Persistent stressful environment and prolonged negative religious intervention might lead to negative transgenerational behaviors. Such transgenerational behaviors might be observed by people who have direct or indirect stakes with the people living in conflict zones and this might redirect for new strategies towards peace and development.
The article is from the print edition of March 8 to 14, 2017.