Epigenetics: nature via nurture
It was thought that DNA has nothing to do with environment. It was thought that our genes are fixed, do not undergo any changes. Yet, we were unable to explain why identical twins when separated at birth, though they carry the exact copy of DNA, had completely different fates: not only socially, but also health-wise. We were unable to determine or explain why people who inherit genes for certain diseases as mental illness or cancer do not necessarily exhibit these diseases. So, the debate of whether nature, that is our genetic make-up, or nurture, that is our upbringing along with the environment contribute to our fate and destiny.
What is now known?
Now we know that environment plays a role in our genetic expression. When we speak about the environment we mean our habits, our upbringing, and our stress levels. The choices we make from what food we eat, what air we breathe, what activities we do, and our overall interaction with the people around us affects our health.
What happens chemically that make these factors influential? To answer this question there is a concept called epigenetics where ‘epi means on or beside’. Epigenetics provide an extra layer of information that can be passed down to future generations.
As we know, turning genes on will lead to their expression, i.e., the production of the proteins necessary for a particular phenotype. Also, turning genes off, known as gene silencing, will lead to some phenotype not being expressed. For example, genes that promote bone growth will be turned off in muscle cells. But how does this happen? There are three systems for silencing genes: DNA methylation, histone modifications, and RNA-associated silencing. Here we will focus on DNA methylation.
What is DNA methylation?
DNA methylation is like adding a tag or flagging certain regions in the DNA with the purpose to affect the transcription of DNA, in particular affecting which genes are expressed and which ones are silenced. This flagging occurs with strong persistent covalent bonds making it a heritable property.
A methyl group is a chemical molecule that has one carbon atom and three hydrogen atoms. These groups attach to the DNA at particular regions known as CpG regions, or cytosine rich regions. Remember, DNA is composed of four nucleotides, A, T, C, G (adenine, thymine, cytosine and guanine). These methyl groups are then inserted or attached to DNA in these CpG regions via specific enzymes called DNA methyltransferases.
This figure created in BioRender.com and taken from the Asian Pacific Journal of Cancer Biology article Epigenetics and Cancer
This methylation causes the DNA sequence at these regions to change appearance and structure, meaning that at these regions DNA is for example more tightly wrapped than before methylation occurs. As a consequence, the modified DNA interacts differently with the enzymes responsible for transcription of genes. This difference is mainly silencing the gene that was supposed to be expressed in the first place.
In the normal functioning of the organism, epigenetic changes contribute to cell differentiation, cell division and cell growth. When these changes or alterations become dysregulated, diseases ensue.
Some cancers arise as examples of epigenetic changes, where DNA methylation is lost, that is, the methylation flags are removed. This loss leads to genes that were supposed to be turned off to be no longer silenced. These genes turned on incessantly will lead to overproduction of proteins causing cancer. On the other hand, too much DNA methylation can turn the protective genes off also contributing to cancer.
For example, colon cancer risk increases with overconsumption of red meat. This is because red meat contains a chemical compound that causes over methylation of DNA, turning off the protective tumour suppressor gene, APC.
In conclusion, it is important to appreciate that our environment contributes to our overall health as much as our genetic inheritance. It’s not nature vs nurture rather nature through nurture.
Takeaways
· Epigenetics is how the environment influences the gene expression.
· DNA methylation is a way where gene expression is altered without altering our DNA sequence.
· Our health not only depends on our genetic make-up but also on the choices we make.
Further explorations
If you find this concept interesting, you can do some further readings about how smoke affects one’s health epigenetically, for example: the following open access review article at BMC is a good read
https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-019-0311-8
Thank you for reading, until next time…