Nearly every cell in our body has a headquarter center called the nucleus. This center stores information about the functioning of the body. Such genetic information is kept in deoxyribonucleic acid, called DNA. DNA takes the form of a two-meter-long chain that is twisted and rolled inside a tiny nucleus. DNA is a fantastic molecule that determines almost all features of the organism. The fact that someone has brown eyes or blonde hair is saved in the DNA. Not only our appearance is hidden in our DNA, but also some predispositions to developing some diseases. How does it work? Thanks to the shortest alphabet having just a few letters written in this tiny nucleus.
The alphabet of a DNA contains just four letters. Credit: Pixabay (Free Pixabay licence)
DNA is built with four kinds of building blocks called nucleobases: adenine (A), thymine (T), guanine (G), and cytosine (C) [1] and related molecules. The sequence or order of these letters determines the information needed to build and maintain a body. Each nucleotide appears in a particular order, just like the letters forming words and sentences. DNA is a long twisted, bundled chain-like structure that looks like a twisted ladder (so-called double helix), and each nucleus contains 6 billion letters (except for female ovarian and male sperm, which has half of these letters). It is so long that if stretched in the linear form, it could be rolled around the Earth hundreds of times!
That unique molecule determines who we are and all details about our body – from the color of eyes and hair to the probability of having particular diseases. DNA contains instructions about who we are that our parents gave us. It works like a hard drive storing data about our bodies. That is how our genome is made. It is one of a kind and consists of 26 chromosomes; each chromosome is a mix of letters with combined proteins, small balls which surround letters. Half of these chromosomes are given to us by our mother and the other half by our father. Chromosomes are divided into smaller segments called genes that carry the aforementioned instructions.
Here, the whole story begins. Each of us has unique combinations of genes which can undergo expression. What does it mean in practice? The expression of genes means that some of them can produce their products called proteins, and some cannot. Each gene produces a particular protein that is specific only to that gene. The production of particular proteins can be controlled by changing the order of letters in the chain of DNA or by environmental factors in epigenetics. Epigenetics is a process when some genes' expression can be changed from external factors like smoking.
A classic example of an epigenetic mechanism is DNA methylation, in which the methyl groups (extra blocks) are added to the DNA to influence the gene expression. These groups are clusters of hydrocarbons attached to the DNA, acting as signals to activate some genetic processes or turn them off. The methylation process requires the presence of some fantastic molecules called enzymes that makes the processes faster or generally possible in our body. When we smoke tobacco, the activity of these particular enzymes is changing what affects the methylation of the DNA. In other words, it also affects particular gene expressions in the body [2].
Even tiny changes to the DNA sequence can have dire consequences. An example of this is the cause of sickle-cell anemia. Hemoglobin is an essential protein in red blood cells. Imagine that one subunit of hemoglobin has more than 1600 bp. When a single base is switched with another base, this subunit has a mutation that causes sickle-cell anemia. Amazingly, one small exchange makes a huge difference. When the mutated DNA is transcribed and translated, the error is carried and in the final amino acid chain instead.
What does it mean in practice? For example, instead of the molecule called glutamic acid, valine is present. That causes the red blood cells to change shape – instead of the usual disc-like appearance, they take on a sickle form. Unfortunately, it impairs the ability of the red blood cells to distribute oxygen throughout the body, which results in the symptoms of anemia [3].
Unfortunately, some genetic diseases have a much broader effect. An example of this type of disease is Bloom Syndrome. This autosomal recessive disorder is caused by a mutation in the BLM gene, coding for the BLM protein, a helicase. The helicase molecule is an enzyme playing an essential role in DNA replication. When a cell divides to form two identical daughter cells, for the parent and daughter cells to be identical, the DNA of the parent cell needs to be duplicated before its division. That happens through a process called DNA replication. Helicases unwind the double helix in this process so that each DNA strand can be replicated.
The BLM protein also plays an essential part in maintaining the stability of the DNA during that process. In the absence of this protein or its damage, the replication process is prone to errors, which results in an extremely high rate of mutations in people affected by Bloom Syndrome. These mutations may cause cancer, very frequent among Bloom Syndrome patients. Other symptoms include short stature, a red rash across the cheeks, mild immune deficiency, and infertility [4].
Mutations in DNA fragments controlling the expression of genes can also lead to disease. Proto-oncogenes and tumor suppressor genes are regulators of gene expression, which, when mutated, can lead to cancer. Proto-oncogenes are sequences promoting the expressions of genes they precede. When the proto-oncogene mutates or has too many copies, it becomes an oncogene. The oncogene is constantly “on,” causing the uncontrolled proliferation of cells, which can form a tumor. Tumor suppressor genes slow down cell division and can induce apoptosis-programmed cell death to eliminate unnecessary cells. When a tumor suppressor gene mutates, it is turned “off” – it cannot stop the division of cells. So they can divide uncontrollably, forming a tumor [5].
Did you know that?
- Each nucleus in the cell contains about 2 m length of DNA.
- Our genes make up only a few percent of the DNA. The rest of DNA plays a regulatory role in gene expression.
- Our DNA differs from the DNA of chimpanzees and bonobos by less than 3%.
- The DNA of the banana differs from the humans’ one by about 60%.
- Mature red cells do not contain a nucleus, so they also do not contain DNA. It is lost during the maturation of the cell [6].
Summary
DNA is a double spring that wraps itself around each other like two ivy shoots. The molecules A, C, G, and T are in the middle of the shoots. The sequence of these four letters can express the code of our organism. Our genetic code comprises approximately 3 billion base pairs and approximately 30 000 genes. Most of them (about 99%) are the same for all humans. An essential feature of DNA is its ability to replicate or make copies of itself. It contains information about the heritage of each individual, even information about the increased risk of certain diseases.
This article is a joint work of Barbara Haber (Faculty of Chemistry, University of Warsaw), Agnieszka Pregowska (Institute of Fundamental Technological Research, Polish Academy of Sciences), Natalia Zawrotna (Faculty of Chemistry, University of Warsaw; Genegoggle, Warsaw), and Magdalena Osial (Faculty of Chemistry, University of Warsaw; and Institute of Fundamental Technological Research, Polish Academy of Sciences) as a part of the Science Embassy project. Image Credit – Magdalena Osial (Faculty of Chemistry, University of Warsaw; Institute of Fundamental Technological Research, Polish Academy of Sciences).
References
[1] Dahm, R., 2008. Discovering DNA: Friedrich Miescher and the early years of nucleic acid research. Human Genetics 122, 565–581.
[2] Martin, E., Fry, R., 2018. Environmental Influences on the Epigenome: Exposure- Associated DNA Methylation in Human Populations. Annual Review of Public Health, 39(1), 309–333.
[3]ter Maaten, J. and Arogundade, F., 2010. Sickle Cell Disease. Comprehensive Clinical Nephrology. In R. J. Johnson, & J. Feehally (Eds.).
[3] Flanagan, M. and Cunniff, C., 2006. Bloom Syndrome. GeneReviews.
[4] The American Cancer Society medical and editorial content team, 2014. Oncogenes and tumor suppressor genes | American Cancer Society. [online] Cancer.org. Available at: https://www.cancer.org/cancer/cancer-causes/genetics/genes-and-cancer/oncogenes-tumor-suppressor-genes.html (Accessed 07 Nov 2021).
[5] Anderson, M. W., Reynolds, S. H., You, M., & Maronpot, R. M. (1992). Role of proto-oncogene activation in carcinogenesis. Environmental health perspectives, 98, 13–24. https://doi.org/10.1289/ehp.929813
[6] https://sciencenotes.org/20-dna-facts-fun-facts-about-dna/ (accessed on 07 Nov 2021)