**1.1 Epigenetics**

For the longest time in the history of scientific research, a belief existed that DNA, the master molecule that makes up our genome, is the destination of living beings, the blueprint for every trait and disease that we might inherit or develop. Various landmark discoveries through many decades contributed to this "ultimate destination" tag of the DNA like the double helical structure in 1953 by Watson and crick, discovery of mutations in certain genes contributing to disease phenotypes such as phenylketonuria, cystic fibrosis, p53, and many more. These developments led to immense interest in the field and one of the most astounding accomplishments in this regard was the "human genome project," which resulted in complete sequencing of the human genome. Soon after, complete genome sequences of closely related organisms and other model organisms were deciphered, published, and made available for use by every researcher across the globe. This led to the inception of the fields of bioinformatics and comparative genetics.

In the middle of all the euphoria about research on DNA and genes, it was being increasingly realized that only about 2% of the DNA in humans codes for proteins. The rest of the DNA was initially called junk DNA. However, an intriguing question surfaced regarding the reason for nature to preserve this huge amount (98%) of junk DNA if it did not serve any function. This seemed quite paradoxical to the concept of evolution.

This question paved the way for more research, and soon interest started booming in the field of epigenetics. This term has been used differently by different scientists from time to time, according to what could be proven using the resources and technology of that time. Epigenetics (from epigenesis) was first aimed to describe changes that take place when a zygote undergoes divisions and leads to differentiation (genesis) into different cell types, tissues, and organs. It was a beautiful concept to illustrate the differentiation potential of zygote, but the knowledge of the mechanisms responsible for this potential was lacking at that time. The term was originally coined by C.H. Waddington in 1942 as the phenomenon that changes the cells from totipotent state to fully differentiated state during embryonic development [1].

The phenomenon of heredity and the concept of genes were not known back then, and hence these definitions did not contain any molecular feature. Later, the term was defined by Riggs as "the study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence" [2]. The most common definition of epigenetics today is "the study of phenomena that lead to heritable changes in gene expression without changing the sequence of nucleotides." For the sake of simplicity and universality, an epigenetic trait was defined as "a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence" at the Cold Spring Harbor meeting in 2008 [3].

All these definitions were based on two important principles.


With the discovery of histones, it was initially thought that these proteins only helped the DNA to wrap itself appropriately to fit into the nucleus. However, with advancing research, histones were viewed as the "interface" between DNA and the environment. These were the proteins that could change the accessibility of genes within the DNA to increase or decrease expression and interestingly, they could do it without the requirement to change the sequence of the underlying gene. This led to the identification of various histone modifications such as methylation, acetylation, phosphorylation, ubiquitylation, and so on, each one of them having their own kind of impact, that is, either increasing or decreasing gene expression. Research performed in the field also showed that different cells carry different combinations of histone modifications, and these combinations together constitute the *histone code*. More research on histones identified mechanisms such as histone sliding that can also influence gene accessibility and expression in response to various signaling pathways and at different stages of the cell cycle. DNA methylation on the 5′ cytosine also came to be recognized as a mechanism that could impact gene expression independent of the sequence of the gene that carries them.

Further research on model organisms was conducted on histones and DNA methylation to establish the transmissibility of epigenetic traits at the molecular level [4, 5]. One of the pioneering experiments performed on the mechanism of epigenetic inheritance was carried out by Manel Esteller and colleagues. The group extensively studied identical twins and verified that twin pairs that were older and/or had experienced different lifestyles had far greater differences in epigenetic marks (histone acetylation and DNA methylation) [6]. These studies were astounding as they helped in establishing the fact that DNA is not the destination to dictate all traits but patterns of expression and epigenetic changes can result in the establishment of different traits as a result of different environments, even in identical twins. Another study showed that supplementation of the diet of expectant mice with vitamin B, folic acid, choline, and betaine could alter the color of the fur of their offspring by affecting DNA methylation of the pigmentation genes [7]. Research on the agouti gene, which can cause diabetes and yellow color pigmentation of the fur in mice, has shown that offspring born to mice that were fed with supplements that resulted in methylation of the gene were slim and nondiabetic due to increased DNA methylation and consequent silencing of the agouti gene [8]. These experiments proved beyond doubt that we not only inherit our parents' DNA but also their experiences and exposures, which influence our traits. Studies performed concomitantly and afterward also showed

*Introductory Chapter: Epigenetics and Optogenetics - The Science behind the Cover Blanket… DOI: http://dx.doi.org/10.5772/intechopen.101190*

how the exposure of mothers to conditions such as smoking, alcohol consumption, stress during pregnancy, prenatal malnutrition, etc., can influence epigenetic patterns of key genes in offspring [9].

The very fact that epigenetic changes are heritable, yet reversible stimulated a lot of interest in the field because it provided a ray of hope to find a cure for many diseases that were initially thought to be terminal. This effect also impacts directly at the level of gene expression and hence can offer a lasting and more effective therapeutic approaches [10]. In addition, it established that different cells carry different epigenetic signatures, and that one cell type can be changed to another, or a *diseased* cell can be converted into a *healthy* one through changes in the epigenetic landscape.

More research identified more players of the field such as long non-coding RNAs, enhancer RNAs, micro RNAs, etc. It was in fact realized that the so-called "junk DNA" actually codes for these "regulator elements," which play a role in regulating the expression of the genes that code for proteins [11]. Until now, we have been able to decipher very little information about epigenetic or regulatory elements. The fact that 98% of the genome codes for regulatory elements prompt us to believe that the field of epigenetics is very diverse and yet mostly unexplored. If this field is explored with the help of more advanced research tools and technology in the future, we might be able to find cures for many debilitating diseases of humans, might find more answers for our similarities and dissimilarities with other species, better understand evolution, and might develop a better understanding of the entire ecosystem by unraveling more connections related to gene–environment mechanisms. Increased knowledge of how gene–environment interactions operate acquired by means of increased knowledge of epigenetics through superior technology might answer many ecologically important questions for us and might enable us to understand the ecosystem and the role of *Homo sapiens* in this ecosystem in relation to other species and the environment more clearly and effectively.
