Of and on, I get readers here and elsewhere asking me questions on the meaning of sequencing, PCR, and structures of the SARS-CoV-2 virus, the various tests for Covid, and about mutations and variants based on these terms.
I thought I had mentioned and explained them in bits and pieces here and there in chat groups, but I still have people asking what these terms are often arising from this Covid pandemic.
I know molecular biology is not for everyone, but for the toughest who evolve as the fittest to survive understanding. Hence our purpose here is to make the understanding of DNA / RNA, about mutation of the virus ridiculously simple for everyone
This simple explanation about DNA or even RNA is dedicated to Dr. Janet LCK my former colleague, and to active, appreciative and contributory participants in my “Golden Ox” WhatsApp chat group.
This may also be shared here for the general lay readers in this blog.
First of all, there are four chemical bases, namely Adenine (A), Thymine (T), Cytosine (C) and Guanine (G) that make up the DNA. Among the four bases, A + T always pair-up as one base pair, and C + G always pair-up as the second base pair.
These pairs are called ‘nucleotides’ which are the building blocks of long strands of DNA or single-stranded RNA, giving the double-stranded DNA a double helix shape when the base pairs in each strand of the DNA are connected.
Viruses can either be made of DNA or RNA. In the case of the SARS-CoV-2 virus it is an RNA polymer, meaning long chains of repeated units of nucleotides.
There are some differences between DNA and RNA, among them generally are:
1. RNA unlike double-stranded DNA is a single-stranded molecules consisting of much shorter chains of nucleotides even though they can by base pairing, form intra-stranded double helixes such as in tRNA.
2. The sugar-phosphate component of DNA contains deoxyribose, whereas the RNA contains ribose. Ribose has a hydroxyl (water) group attached to the pentose ring in the 2' position, whereas deoxyribose does not. The hydroxyl groups in the ribose backbone make RNA more chemically labile than DNA by lowering the activation energy of hydrolysis.
3. In DNA, the complementary base to adenine in DNA is thymine, whereas in RNA, it is uracil, which is an unmethylated form of thymine.
Hence, we shall use the DNA model instead of RNA because most people have heard of and understand DNA more than RNA. Furthermore, most of the organisms are made of DNA rather than RNA.
Hence, using DNA as a model makes it more generally applicable. This makes it easier for us to understand, and can be applied for RNA-based organisms also as in the case of SARS-CoV-2 virus which is a polymer structure of RNA only as already mentioned.
Of course the molecular structure of the Covid virus is not a double helix DNA.
As already explained, it is an RNA with a single-stranded (positive-sense) RNA associated with a nucleoprotein within a capsid composed of matrix protein, but we shall not complicate this explanation here.
However, the CoVs virus has the largest RNA viral genome, ranging from 26 to 32 kb in length.
We shall instead of using the RNA for this SARS-CoV-2, we shall use DNA for general purpose as in molecular biology to represent the RNA also.
The pairing is the base by which the DNA is copied when cells divide. The entire length of the DNA is called the genome, and they can be very long. For instance, the human genome consists of 3 billion base pairs arranged in various ways called ‘sequence’.
The base pairs provide instructions on how the structure of the organism ought to be, and how they should function and maintain.
The sequence also provides the genetic information that is carried in a particular segment of the DNA. For instance, sequencing provides information on which stretches of DNA contain the genes and which stretches carry regulatory instructions like turning genes on or off.
Furthermore, the sequence data can show changes in a gene that may cause disease or cause an organism or a virus like the SARS-CoV-2 to change or to mutate.
If there is any change in the sequence or ‘arrangements’ of the nucleotides in the DNA or RNA this is called ‘mutation’.
The Music of Life:
Evolution of life through mutation of RNA / DNA is like writing a musical composition.
Firstly, in music there are only 7 notes, namely: A B C D E F G
If these notes whether neutral, sharpened or flattened are randomly arranged on a musical scale whether on the treble or bass clef, they will produce a mixture of sounds which may be pleasant or unpleasant to the ears. That technically is music. Further emergence of the sounds of music may be produced using different arrangements or repeating them an octave higher or lower.
An octave, in music, is an interval whose higher note has a sound-wave frequency of vibration twice that of its lower note. The international standard pitch A above middle C vibrates at 440 hertz (cycles per second); the octave above this A vibrates at 880 hertz, while the octave below it vibrates at 220 hertz.
If we arrange the A B C D E F G sequence of these musical notes whether an octave higher or lower, with or without the notes being sharpened a little higher, or flattened a bit lower in different ways in a planned order, we get a musical composition coming out of these arrangements as much as we use the alphabets from A to Z in different combinations to construct meaningful words, and sentences. We then get a story evolving like what we are now typing and reading.
It is a matter of how we arrange them to get music out of them.
Let us now imagine each musical note in the scale represents the nucleotides and only 4 bases consisting of adenine (A), cytosine (C), guanine (G), and thymine (T).
If these 4 bases are arranged in a certain sequence, we get an RNA or the double strand DNA emerging.
If there are any changes in the sequence of these musical notes, the alphabets in a word, or the bases in RNA / DNA we get different types of music, stories, or species of life emerging out of these planned or randomized arrangements.
This is exactly how different types of life are evolved through variations in the mutations which is just any change in the sequence of the nucleotides of an DNA
Hence, we can clearly see the similarity between different music, different stories and different life evolving by merely changing the positions or the sequence of A B C D E F G notes for music, A – Z for sentences, and A C G T bases for an RNA / DNA to be composed.
For words, sentences and stories we may need or may not need all 26 alphabets, for music only 7 notes, and for all tens of millions of lives on Earth only 4 bases of their DNA.
Hence, music is similar to the evolution of life, conversely, life is similar to music.
In short, evolution is nothing but just the composition of the music of life.
By changing the order or sequence in a DNA, it will give rise to a new strain of an organism, and if this is done multiple times by random chance due to environmental threats to their existence, or to their continued survival, as probably have happened since 3,500 million of years ago, they give rise to different species of life in the course of evolution, especially between 542 – 488 million years ago during the Cambrian Radiation when there was an explosion on the biodiversity of life on Earth.
Viruses may have already existed 3,800 million years ago when the first RNA world shown by the first chemical fossils came into being, and it was not until 3,600 million years ago the first DNA protein life came into existence
In fact, mutation is the key to how various life came into existence. It was these mutations over the course of 3,600 million years that the history of life was naturally written out like a story.
In the same vein, the order in which we change the sequence or arrangements of the base pairs, we get different types of diseases emerging, or the mutations of the Covid virus into variants, especially if we threaten their natural sequence with antiparasitic drugs like antimalarials like chloroquine, hydroxychloroquine, antiparasitic ivermectin, antivirus drugs like remdesivir, lopinavir, and other HIV protease and nucleotide inhibitors like ledipasvir, and even with baricitini used for treating rheumatoid arthritis.
Similar changes will occur if we attempt to keep this virus in check with various types of vaccines when different types of antibodies elicited will force them to change their mutagenic-pathogenic profiles. This is how the power and might of Nature operates to keep all life on Earth in check and balance
These challenges with drugs, social distancing, lockdowns, movement restrictions, quarantines, face masks only threaten the virus existence, causing them to become more adaptable by mutating into the fittest variants for them to continue to exist and survive.
Thus, sequencing means determining the order of the four chemical building blocks - called "bases" - that make up the DNA molecule, and it is this sequencing we are able to determine whether or not the virus has mutated into various variants as we can see clearly see the emergence of various variants in the Covid-19 since this pandemic emerged in the late of December 2018.
I hope we manage to explain in the simplest way for ordinary lay readers although I need to apologize for using the arrangements or sequence of A – Z alphabets as an analogy which may not be quite technically correct as there are 4 bases, not 26 bases. The principle remains the same.
This analogy is the best we can do to demonstrate multiple mutations of alphabets into words, and from words into sentences, and from sentences into a simple explanation / story like this one for illustration.
This is also how the first life was evolved into biodiversity, and so shall this virus if we are not careful but continue to challenge its existence with various drugs and unnecessary vaccines.
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