Transcription and Translation

Extract from “The Alternative Life” (1996)

Before I draw my own conclusions about the communication of habits, there is yet another fundamental mystery at the heart of biology that I can best exemplify by looking again at the processes of transcription and translation from the point of view of spatial logistics within a eukaryotic cell.

The need arises within the main body of the cell for a particular enzyme in order to either degrade a type of surplus molecule or manufacture a deficient one. A message is somehow communicated to the nucleus which causes a chromosome to unwrap its protein sheath and open up a loop in its DNA strand at exactly the right place. Opening up a loop is like pulling the two strands of a piece of rope apart in the middle. Since the base pairs are on the inside of the double helix and the whole helix is coiled up and wrapped in protein, there should be no external indication of what lies within. Seemingly, something in the cell knows that it has the ability to satisfy the need and furthermore knows exactly where to find that ability. It doesn’t try everything until it finds the right cistron, if it’s there at all; it goes straight to it, which indicates memory. The sequence of exposed bases in the exposed cistron of DNA is read by an enzyme in much the same way that DNA replication occurs but with several important differences.

Firstly, only one of the two strands that are exposed is read. (It is worth noting that, when a strand of DNA and the appropriate nucleotides and enzymes undergo transcription in a test tube, both strands are read). Secondly, as soon as the counterstrand has been made, it detaches itself. Thirdly, several copies of the counterstrand are usually made in quick succession. Fourthly, the nucleotides that are picked up are not deoxyribonucleotides but ribonucleotides, which differ only by the presence of one extra oxygen atom in the sugar part of the molecule (though, on a point of technicality which is indicated by the names, deoxyribose actually has an oxygen atom missing from ribose). Lastly, although three of the nucleotide bases are the same, thymine is replaced by uracil (U), which differs from thymine only by the absence of a methyl group. They both have the same hydrogen-bonding characteristics. Once read, the DNA loop closes up again to re-form a double helix and the chromosome wraps itself up again.

In the nuclei of eukaryotic cells there are only ribonucleotides so there is no potential confusion during transcription. However, during DNA replication in eukaryotic cells and in prokaryotic bacteria at all times, the chemical environment must contain both ribonucleotides and deoxyribonucleotides, but only the ribonucleotides are selected to make strands of RNA and only deoxyribonucleotides are selected for replication. The chemical and morphological differences between ribonucleotides and deoxyribonucleotides are minimal. In laboratory experiments, they readily become linked to each other.

The result of the transcription process is several single strands of RNA, which leave the nucleus and make their way to a ribosome in the main body of the cell. The code in an RNA strand is the exact counterpart to the code in the cistron of DNA, which means that -TAC- in DNA transcribes as -AUG- in RNA. There are three main types of RNA. The type that goes on to code for proteins is called messenger RNA, or m-RNA. The site of translation is the ribosome, which is a small globular entity made of protein and ribosomal RNA, or r-RNA. Each m-RNA strand passes over a ribosome and picks up molecules of transfer RNA, or t-RNA, which are milling around the ribosomes. There are several different types of t-RNA, each of which has an exposed site which is the appropriate codon to be attracted to its counterpart codon on the m-RNA. For example, where the m-RNA read -AUG- the attracted piece of t-RNA reads -UAC- at its exposed site, which becomes hydrogen-bonded to the m-RNA codon.

Transfer RNA molecules are a bit like loyal horses, since each different type of t-RNA carries a different type of amino acid. For instance, the rider on a t-RNA molecule which reads  -UAC- at its exposed site is always a tryptophan molecule. As the molecules of t-RNA assemble in order on the m-RNA, the amino acids become bonded together through peptide bonds, like handcuffing riders together as their horses line up in position at the starting blocks. As each peptide bond is made, the t-RNA molecule loosens its grip on the amino acid and also drops off the m-RNA, like each horse in turn throwing its rider and bolting. (Maybe they’re not so loyal). Each t-RNA molecule then collects another appropriate amino acid. Molecules of t-RNA do not try to get themselves translated into proteins any more than m-RNA strands try to pick up amino acids; they both seem to know their functions, despite there being no tangible difference between them.

The strands of m-RNA pass over the ribosome in turn as a continuous progression, to translate their whole coded messages into proteins; they do not shuffle back and forth or break away in mid-passage. Once a strand of m-RNA has passed over the ribosome it is rapidly broken down into its constituent nucleotides by enzymes. Those enzymes do not degrade m-RNA strands before they pass over the ribosomes, nor do they degrade t-RNA strands, yet they all exist within the vicinity of the ribosome. The ribonucleotides make their way back to the nucleus while the enzymes seek out the molecules that they have been created to chemically change, and do their job. The situation is further complicated by the fact that many reactions in the cell require energy. This is not supplied by heat. It is usually supplied by the conversion of a high energy molecule called ATP into a lower energy molecule called ADP or an even lower energy molecule called AMP. ATP molecules can supply jolts of energy wherever they are needed in the cell. The energy-requiring reaction and the energy-supplying reaction both have to happen at the same time and place.

The size of a relatively large molecule, like an RNA strand or an enzyme, in relation to a cell is comparable with a mustard seed inside a large beach ball. There are thousands of different types of molecule inside any cell and millions of molecules in total. The number of strands of m-RNA and the number of enzyme molecules are very few. The number of substrate molecules may also be very few. This is not chemistry as we have come to understand it in laboratories. It is not based on random collisions which may or may not result in interactions. Every reaction that happens in cells obeys the rules of chemistry in terms of what is permissible, but it is selective chemistry based on organisation and order, like the way that scientists do selective chemistry in a laboratory. What is most remarkable about cell chemistry is not so much what does happen as all the things that don’t happen. That requires selection. Only at the moment of death of a cell does random equilibrium chemistry take over. The only adequate definition of death is absence of life.

If you were to wait for all the interactions that occur during transcription, translation and resultant enzyme-catalysed reactions to happen through chance encounters, you’d have to wait an eternity. Consider the time it takes for something you see, hear or feel to evoke responses like fear, anger, relief, sexual arousal or physical movement in your body. These responses often involve changes in your body chemistry which require the action of enzymes on a co-ordinated basis in many of your body cells. What’s more, all those responses have a non-chemical origin. I have just looked at one aspect of cell chemistry. When you put together the thousands of complex chemical reaction sequences that simultaneously occur inside every cell, it is apparent that there is nothing random about cell chemistry; it is ordered, organised and co-ordinated in such a way that every cell, chromosome and molecule knows what it has to do and when it has to do it. All the above may seem fairly obvious if you regard life as being miraculous but many molecular biologists are determined to make us believe that life is merely a consequence of natural interactive chemistry. In their view, life is not only the cause of cellular interactions but also the effect. That begins to sound like another perpetual motion machine.

2023 Postscript – The Genetic Code

DNA famously consists of a double helix, the outside of which is constructed from two continuous sugar-phosphate chains. On the inside are two long sequences of four different types of nucleoside base (A,C,T and G) which are physically connected to the sugar-phosphate chains and ‘attracted’ to their opposites (in the other helix) in a complementary way (such that A complements T and C complements G). That makes for easy replication or transcription. During transcription a DNA double-strand opens up a loop (like pulling apart a piece of double-stranded string in the middle) and a section of only one strand is ‘read’ by an enzyme, with very definite starting and ending points, to produce a strand of RNA. The issue of the precise starting point is crucial, though every base is chemically equivalent and hence a potential starting point. That is done in the nucleus (or DNA storehouse), and all RNA strands thus produced are transported into the main body of the cell.

RNA differs from DNA insofar as it uses a slightly-different sugar in its chain, it doesn’t form double helices and it uses the nucleoside base U instead of T. There are several different types of RNA, the most important of which are many thousands of different messenger-RNAs (each corresponding with a different specific protein molecule) and approximately 20 different transfer-RNAs (each of which ‘collects‘ a different amino acid to take to the protein assembly line, called a ribosome). By an incredibly complicated, but also very reliable, procedure, each m-RNA strand is translated into its specific protein molecule by passing over a part of the ribosome (like magnetic tape passing over a tape head). This happens because every three nucleoside bases in m-RNA forms a triplet codon which ‘attracts’ a particular t-RNA strand (which ‘carries’ a particular amino acid) and the protein strand is formed by connecting the amino acids together in sequence within a ‘tunnel’ in the ribosome. Once the m-RNA strand has been translated, it is degraded by an enzyme into its constituent nucleotides, which are transported back to the nucleus.

For over thirty years, it has seemed to me that there are three separate and distinct ways to interpret the origin and retention of these processes, though each may have slightly different variations. They approximate to religious, philosophical and scientific views. I ask you to consider which is the most preposterous and which is the least preposterous.

  1. That a pre-existing, omnipotent, omniscient entity, usually known as God, deliberately and purposively created the genetic code and the processes of transcription and translation. Their retention is due to omnipotence.
  2. That an emergent, experimenting entity, with memory, happened to create those practices by getting down amongst the molecules, and retained them through habit amongst all descendants. The words that could be used to describe this entity include mind, spirit, soul (usually exclusively associated with humans) and life.
  3. That those practices were created spontaneously by automatic chemistry, and they continue because that is what automatic chemistry necessitates. Under this materialist scheme, life, consciousness and possible free will are all by-products of physico-chemical interactions. Life is an effect rather than a cause.

See also “Crossover in meiosis”.