On The Concept of Genetics, And What It Entails In Our Lives.
The idea of “genetics” has been brought up loosely these days.
Dr Joel Yong
The idea of “genetics” has been brought up loosely these days. A lot of people don’t even understand what they mean when they say things such as:
- “He/she looks so physically attractive. They have good genes.”
- “I’m lazy. My parents were lazy. Hence, laziness is genetic.”
- “(Insert abnormal condition here) is caused by abnormal genetics.”
- “It’s in our DNA to be (insert positive descriptor here).”
What, even, is a gene?
The idea of DNA and what it represents
Our bodies comprise roughly 38 trillion cells, which differentiate into different cells to support the function of different systems in the body. For example, in this article Why Does Osteoporosis Affect Post-Menopausal Women More Significantly Than Other People?, I touch on the fact that our bones contain 3 major types of cells — the osteoblasts, which form new bone mineral, the osteoclasts, which dissolve old bone mineral, and the osteocytes, which are osteoblasts that are entrapped within the bone mineral content that they have produced.
An osteoblast does not turn into an osteoclast at the snap of a finger — otherwise we’d all be suffering from osteoporosis or brittle bones. There is a controlling mechanism involved in preventing that sort of evolution.
It lies in the identity of the cell, which is provided by its deoxyribonucleic acid (DNA) identifier.
DNA is a molecule comprising two polynucleotide chains that is arranged in a double helix manner. The polynucleotides contain simpler nucleotide molecules that interact and bind with each other. There are 4 main nucleotides: cytosine (C), guanine (G), adenine (A) and thymine (T). These nucleotides form either C-G or A-T base pairs, which form the structure of the double helix.
It is estimated that the entire human genome contains 3 billion C-G and A-T base pairs.
The information that is contained in these base pairs provides cells with their ability to synthesise biochemicals that are important for signalling within the body, such as proteins. A normal gene in a human cell contains 27000 base pairs, though some can go up to be as big as 2 million base pairs. Therefore, the human genome contains 3 billion base pairs to encompass all the different genes and functions that our body needs to survive and thrive. These genes tell the cell what proteins they ought to be synthesising:
In the genetic code, each group of three nucleotides — known as a “triplet” or “codon” — stands for a specific amino acid. For example, GCA stands for alanine, AGA stands for arginine, and AGC stands for serine. There are 64 possible codons, but only 20 amino acids, so more than one codon may code for a single amino acid. For example, GCA, GCC, and GCG all mean alanine.
For example, parietal cells in the stomach contain genes to produce carbonic anhydrase enzymes. Carbonic anhydrase supports the production of acidic hydrogen ions (H+) from bicarbonate ions, and that is how the stomach can produce acid for food digestion.
When it is time for a cell to replicate, the information from the DNA molecule is copied as such:
When a cell needs to copy a DNA molecule, it “unzips” part of the double helix, breaking the rungs of the ladder in half so that the molecule separates down the middle. New nucleotides, floating free in the cell, can then hook up with complementary nucleotides along each strand. Gradually the unzipping proceeds, and the new strands continue to grow until one DNA molecule becomes two identical DNA molecules.
This mechanism is catalysed by the DNA polymerase enzyme, which connects free nucleotides with the existing nucleotides in each strand.
That’s what is IN our DNA, from a purely biochemical standpoint.
Some genes will be dormant in some cells. Not all parts of the human genome are active in every cell. Otherwise a liver cell can easily just take on the function of a brain cell, for instance.
We don’t want that. We desire an optimum number of cells functioning healthily in our organs – that’s what makes up a healthy functioning human body!
How do things go wrong genetically, then?
The copying mechanism can go wrong as information is transmitted from the sperm cell of the father and the egg cell of the mother to the development of the foetus in the mother. With the billions of base pairs that are being copied, we can’t ensure that DNA polymerase will get things right all the time. It is very much like a photocopying machine, where repeated copies of a photocopy results in the quality of the subsequent copies to be visibly diminished.
Instead of C-G or A-T coupling, we can sometimes see the formation of odd C-A or G-T pairings. We can also see possible insertions of new base pairs or deletions of original base pairs, which exacerbate the copying mechanism’s errors further.
If most base pairs are lined up and copied correctly from the DNA of both parents while synthesising the DNA of their child, the child should not be born with visible health problems. However, encoding errors can result in birth defects or the child being born with “genetic” disorders — things that cannot be cured because the child was borne out of a defective DNA copying mechanism.
For example, cleft palates in children can be attributed to errors in DNA synthesis and replication.
Hence, some people can be born with cleft palates. As multiple genes contribute to the risk of developing autoimmune diseases, it also isn’t surprising to see children born with issues such as Type 1 diabetes either.
It’s all a matter of faulty DNA replication.
It’s not even the fault of the parents. They may be the healthiest and fittest men and women on the planet, but even that does not reduce the probability of their children being born with no defects down to ZERO.
Another way would be the misrepresentation of codons. If we have 64 different codons that encode 20 amino acids, the erroneous insertions or deletions can contribute to an encoding of malfunctioning proteins.
As most of these proteins require specific configurations and structures to be at their most efficient performance levels (which I do cover in the lock and key mechanism at Unlocking The Lock And Key Mechanism That Governs Our Body’s Cellular Functions), an erroneous encoding could lead to the development of a faulty “lock” in the protein that either refuses to work with the correct key, or works with the wrong key, which isn’t good for the body either way.
Having a defective gene that we’re born with will also result in problems with our cellular functions. For example, some people have a defective methylenetetrahydrofolate reductase (MTHFR) gene, which results in the body’s inability to regulate homocysteine levels when the defective MTHFR genes are not producing enough MTHFR to deal with the homocysteine. This is considered to be important because homocysteine:
was also found to stimulate IL-1β production by human peripheral blood monocytes and TNF-α production by monocyte-derived macrophages.
Even if we aren’t born with it, we may still develop it later on (lifestyle choices).
Our cells are constantly reproducing and forming new cells. Each replication cycle brings on a new probability of copying errors. It is up to the immune system to eliminate defective cells via autophagy (phagocytosis). Digest them up, so that their nucleic acid material can be recycled and repurposed to synthesise the next cell (hopefully with less major defects).
How well autophagy operates, therefore, is dependent on the efficiency of the immune system in eliminating those cells. When autophagy is working fine, we can eliminate them more quickly. Crisis averted. However, I do illustrate Four Ways That Our Lifestyle Affects Our Immune System, which indicate how our lifestyle can affect the functionality of our immune system, which will then affect the autophagy process and the subsequent clearance of defective cells from the body.
Lifestyle choices can also result in damaged DNA. I will illustrate that with 2 examples: (1) the consumption of charred grilled foods and (2) overexposure to ultraviolet radiation from the sun.
Firstly, charred grilled foods.
When we grill foods at high heat over an open flame that is hot enough to cause a charred surface, the charred surface will end up containing polycyclic aromatic hydrocarbons (PAHs) such as benzopyrene.
Now, benzopyrene on its own does not cause any problems.
However, this research article shows that it is converted by the liver into a highly reactive epoxide. The epoxide can then react with and oxidise DNA molecules in cells, thus causing a change to the structure of the DNA molecule.
We do have the nuclear respiratory factor 2 (nrf2) transcription factor that upregulates genetic activity for producing more glutathione antioxidant enzymes within the cell — this glutathione can neutralise the epoxide before it causes damage.
Otherwise, if the cell DNA were damaged… Now, if autophagy were working fine, the cells with the damaged DNA molecules ought to be cleared off pretty quickly.
However, if one’s autophagy mechanism is dysregulated, then the clearance of these affected cells will proceed more slowly, resulting in an accumulation of cells with oxidised DNA in the body.
What would be the problem, then? If crucial genes are affected in the oxidised DNA segments, then these cells won’t be producing the necessary proteins that the body needs to function, but are simply lazing there as dead weight. If they can’t be eliminated quickly enough, but continue to multiply into a nice visible mass… that’s the formation of a cancer tumour right there.
And cancer patients are known to have higher levels of DNA oxidation, as evidenced in this paper.
Secondly, overexposure to ultraviolet (UV) rays.
Our skin contains many different organic molecules with different chemical structures. Some of these molecules are sensitive to UV rays and can release electrons or generate free radical species that are highly oxidative and damaging to DNA molecules in a process known as photosensitisation. The use of paraben (parahydroxybenzoate) preservatives in skincare products adds further to the likelihood of damage as the aromatic (benzene) rings in the paraben molecules are also susceptible to photosensitisation.
Overexposure to the sun can cause problems — but having parabens in skincare products that supposedly are meant to protect your skin would also result in the development of the problem that one was trying to avoid in the first place.
Do our genes predispose us to be more susceptible to chronic inflammatory diseases, then?
The human genome contains so many different genes, as I have mentioned earlier. What do we mean when a disease is “genetic”?
I have highlighted the developments of various different chronic inflammatory conditions, which can be examined here:
- Osteoarthritis: What The Deuce Is Different Between Osteoarthritis and Rheumatoid Arthritis?
- Type 2 Diabetes: Type 2 Diabetes — A Case of The Immune System Gone Bad, Too?
- Heart Disease: Now Seriously, What’s So Tricky About Cholesterol?
- Neurodegenerative Disease: Brain Degeneration Ain’t All That It’s Cracked Up To Be
- Osteoporosis: Why Does Osteoporosis Affect Post-Menopausal Women More Significantly Than Other People?
- Hypertension: You Don’t Have To Be Pressured About Hypertension — Or Do You?
In these situations, the symptoms of the condition arise from a transcriptional pathway in the cell known as nuclear factor kappa B (NF-κB), which regulates the transcription and expression of genes that produce pro-inflammatory cytokines. In Four Ways That Our Lifestyle Affects Our Immune System, I do show how NF-κB activity can be upregulated by poor lifestyle choices, and as such can cause a dysregulation in the expression of pro-inflammatory cytokines such as IL-1β and TNF-α, which then signal our cells to behave differently from what they normally do.
For example, in Type 2 diabetes, an elevated expression of pro-inflammatory cytokines will cause cells to disregard the insulin signal for glucose uptake in a situation that is known as insulin resistance, which results in the accumulation of glucose in the blood and the subsequent symptom of an excessive blood glucose concentration, which we can then term as diabetes.
Of course, we do have the nuclear respiratory factor 2 (nrf2) transcription factor that I have discussed earlier, which acts as a counterbalance for NF-κB activity. Having “good genes” might mean that the glutathione production capacity is stronger in one person than another, and that’s one possible reason as to why some people can smoke that many cigarettes and not suffer lung cancer.
Are these chronic inflammatory diseases “genetic” then?
Yes, we can argue that the transcription factors increase the genetic activity in the cellular overproduction of undesired biochemicals.
But where does this genetic activity come from?
Were we born with it, or can we prevent its dysregulation with healthy lifestyle choices?
Prevention is better than cure — but take note, prevention also does not mean that the risk of developing these issues goes down to a perfect zero, either.
Genes are segments of our DNA code that empower cells with the capability to synthesise different proteins and enzymes that are used for various functions.
People who are born with hereditary diseases have errors in their DNA replication mechanism that could not have been predicted ahead of time and that definitely could not be regulated or controlled by human hands.
However, being born with a well functioning DNA code does not mean that we can live our lives with reckless abandon. Poor lifestyle choices can always catch up with us 30, 40, or 50 years down the road to hit us with multiple whammies of different degenerative diseases — it isn’t so much of a genetic predisposition towards it as a it is a matter of the control being more in our own hands!
Joel Yong, PhD, is a biochemical engineer/scientist, an educator and a writer. He has authored 3 ebooks (available on Amazon.com in Kindle format) and co-authored 6 journal articles in internationally peer-reviewed scientific journals. His main focus is on finding out the fundamentals of biochemical mechanisms in the body that the doctors don’t educate the lay people about, and will then proceed to deconstruct them for your understanding — as an educator should.
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This article was originally published by Dr joel yong on medium.
Dr Joel Yong
Deconstructing the interconnectedness between health and business. Join my mailing list at http://thethinkingscientist.substack.com or book a one-on-one consultation session with me at https://app.ddichat.com/experts/thethinkingscientist.