“The genetic code is the key piece of life, which in the case of humans stores the information that allows the body to develop among the nearly 20,000 genes that make up the genome. All the cells of the same body have the same DNA.”
So how is it possible that they act differently? Or rather, how a neuron is a neuron and not a hepatocyte, if they present the same DNA? The answer lies in epigenetics.
What is epigenetics?
Although it contains the information, the chain of deoxyribonucleic acid is not everything, since there is an important component that is the environment. Here comes the term epigenetics, “about genetics” or “besides genetics”.
There are factors external to the genetic code that regulate the expression of different genes, but always keeping the DNA sequence intact. It is a mechanism that has its relevance: if all the genes were active at the same time it would not be any good, for which a control over the expression is necessary.
The term epigenetics was coined by the Scottish geneticist Conrad Hal Waddington in 1942 to refer to the study of the relationship of genes and environment.
A simple way to understand epigenesis was given to me by a good friend with this example: if we think that DNA is a library, genes are books and gene expression is the librarian. But the libraries themselves, the dust, the shelves, the fires … everything that hinders or helps the librarian to access the books would be epigenetics.
The human genome consists of more than 20,000 genes, but these are not always active at the same time. Depending on the type of cell it is, at what stage of development is the organism or even the environment where the individual lives, there will be some active genes and others will not. The presence of a group of proteins that is responsible for controlling gene expression without modifying the DNA sequence, that is, without causing mutations or translocations, for example, allows this.
Knowing the epigenome
The concept of epigenome was born as a consequence of the appearance of epigenetics, and is not more than all the components that are part of this regulation of gene expression.
Unlike the genome, which remains stable and immutable from birth to old age (or should be), the epigenome is dynamic and variable. Throughout the development it is changing, it can be affected by the environment, and it is not the same according to the type of cell. To put an environmental effect, it has been seen that consuming tobacco has a negative impact on the epigenome, which favors the appearance of cancer.
Before continuing, a brief review of genetics is needed to understand the purpose of DNA. The genetic code contains genes, but for that very reason this would have no consequences. In general, it is necessary that a protein complex called RNA polymerase “read” this gene and transcribe it to another type of nucleic acid chain called “messenger RNA” (mRNA), which only consists of the gene fragment read.
It is necessary that this obtained RNA be translated into the final product, which is none other than a protein, formed by another molecular complex known as ribosome, which synthesizes the protein from the mRNA.
DNA is a very large structure, which in the case of humans has a length of almost two meters, much greater than the diameter of any cell.
Nature is wise and found a method to drastically reduce the size and package it inside the nucleus of the cell: thanks to structural proteins called “histones”, which are grouped in groups of eight to form the nucleosome, they support the chain of DNA so that it coils in it and facilitate folding.
The DNA chain does not compact completely, leaving more free parts for the cell to carry out its functions. The truth is that folding makes reading of genes by RNA polymerase difficult, so it is not always folded in the same way in different cells. By not allowing access to RNA polymerase, you are already exerting a control over gene expression without modifying the sequence.
It would be very simple if it were only this, but the epigenome also makes use of chemical markers. The best known is DNA methylation, which consists of the binding of a methyl group (-CH3) to deoxyribonucleic acid. This mark, depending on its placement, can both stimulate the reading of a gene and prevent it from being reached by RNA polymerase.
Is the epigenome inherited?
The genome, which is invariable, is inherited from each of the parents of an individual. But does the same thing happen with the epigenome? This topic has brought a lot of controversy and doubts.
Remember that, unlike the genetic code, the epigenome is dynamic. There are scientific groups that are convinced that it is also inherited, and the most recurring example that is exposed is a case of a village in Sweden where the grandchildren of grandparents who experienced famine live longer, as if it were the result of epigenetics.
The main problem with this type of studies is that they do not describe the process, but are only conjectures without a demonstration that solves the doubt.
As for those who believe that the epigenome is not inherited, they are based on a study that reveals a family of genes whose main function is to restart the epigenome in the zygote. However, the same study makes it clear that the epigenome does not restart completely, but that 5% of genes escape this process, leaving a small door open.
The importance of epigenetics
The importance that is being given to the study of epigenetics is that it can be the way to investigate and understand vital processes such as aging, mental processes or stem cells.
The field in which more results are being obtained is in the understanding of cancer biology, looking for targets to generate new pharmacological therapies to fight against this disease.
As mentioned earlier in the text, the epigenome in each cell changes according to the stage of development in which the person is.
There are studies that have proven this. For example, it has been observed that the genome varies in the human brain from birth to maturity, while in adulthood until well into old age it remains stable. During aging there are changes again, but this time downward instead of upward.
For this study they focused on DNA methylations, seeing that they generated more during adolescence and descended in old age. In this case, the lack of methylation hinders the work of RNA polymerase, which leads to a decrease in efficiency on the part of the neurons.
As an application for the understanding of aging, there is a study that makes use of DNA methylation patterns in bloodline cells as indicators of biological age. Occasionally, chronological age does not coincide with biological age, and with the use of this pattern one could know the patient’s health status and mortality in a more concrete way.
Cancer and pathologies
Cancer consists of a cell that for some reason ceases to be specialized in its tissue of origin and begins to behave as if it were an undifferentiated cell, without limiting its proliferation or moving to other tissues.
It is common to think that changes in the epigenome can cause a cell to become cancerous by affecting gene expression.
In the DNA there are genes that are known as “cancer suppressors”; its own name indicates what its function is. Well, in some cases of cancer it has been seen that these genes are methylated so that they inactivate the gene.
Currently, the aim is to study if epigenetics affects other types of pathologies. There is evidence to suggest that it is also involved in arteriosclerosis and in some types of mental illness.
The pharmaceutical industry has its eyes on the epigenome, which thanks to its dynamism is a feasible target for future therapies. Treatments are already being implemented in some types of cancer, mainly in leukemias and lymphomas, where the drug is aimed at DNA methylation.
It should be noted that this is effective as long as the origin of the cancer is epigenetic and not another, as for example by a mutation.
However, the biggest challenge is to obtain all the information about the human epigenome, by way of sequencing the human genome. With a broader knowledge, in the future more personalized and individualized treatments could be devised, since we can know the needs of the cells of the damaged area in a specific patient.
Science needs time
Epigenetics is a fairly recent field of research and further study is needed to understand the subject more.
What must be clear is that epigenetics consists of regulation of gene expression that does not modify the sequence of DNA. It is not uncommon to find wrong references to epigenetics in cases of mutations, for example.