The Genetic Code is Amazingly Designed

The unfathomable number of parts in a living system

The complexity of even the simplest living cell is beyond imagination!

The body of a living creature is an engineering marvel that has millions of trillions of part. For example the human body has 30-40 trillion human cells, apart from at least the same number in bacteria (or see the nature pdf here). Each cell has tens of millions of parts. For example, a yeast unicellular organism, which is a simple eukaryotic organism, has 42 million protein molecules alone, according to a study (or see pdf here), apart from nucleic acids, lipids, and carbohydrates!

This myriad of interacting part, enclosed inside the complex cell-membrane of the living cell, and in many cases compartmentalized in sub-cellular compartments in the case of Eukaryotes, form a hyper-sophisticated mesh of chemical interactions. Humanity is scratching the surface of understanding what is happening in the living cell, and how those parts interact together to deliver the required functionality.
One thing we do know, is the critical role of proteins in the living system, whether in building the cell, delivering functionality, or acting as enzymes catalyzing chemical reactions, or acting as molecular motors propelling the cell, or moving cargo around inside of it.

The Central Dogma of Molecular Biology

Another thing we know, is that this multitude of proteins is manufactured through the transcription-translation process; a process involving DNA, RNA, and a myriad of enzyme complexes that yield the required product; proteins.

The so-called central dogma of molecular biology is an explanation of the flow of genetic information within a biological system. It is often stated as “DNA makes RNA, and RNA makes protein”,^[1] although this is not its original meaning. It was first stated by Francis Crick in 1957,^[2][3] then published in 1958:^[4][5]

The Central Dogma. This states that once “information” has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein. (Read more about it here: https://en.wikipedia.org/wiki/Central_dogma_of_molecular_biology).

Primarily, Biological information has three main processes:

1. DNA Replication, essential for cell division.
2. DNA transcription, which produces RNA from DNA.
3. RNA  translation, which produces the required protein.

There are other process that also transfer biological information, Reverse transcription, and RNA replication, but we will not address them here, and rather focus on the primary processes above.

A super-computer inside each organism!

So, we have this ultra-huge number of parts, and trillions of cells that make a living creature function; so will we here understand how this happens through understanding the genetic system? No! Because actually humanity still has a very long path to find out. But we will explain in very simple language the basics of how the genetic system works just to produce proteins; a process that is also far from being fully understood, with more and more being discovered about the complexity and intricacy of this system every day.

Beyond the genetic system, there is the over-arching macro control mechanisms that actually determines what the creature (for example an animal) needs to do in any certain context, and then through a series of action-reaction chains, at the foundation level, a signal will be captured by a set of cells that will trigger the genetic system to start, for example, producing a certain protein, and the magic starts.

In this article, we will use an analogy for the Genetic system in its path to produce proteins, as if there is a computer system in the cell that manages this process:

1. The DNA material on chromosomes is analogous to a storage cluster of hard-drives in a data center on which the software that runs the cell is stored.
2. Upon cell replication, the whole storage system is replicated and copied to a new cell by a faithful data replication mechanism!
3. Epigenetics, histones, acetylation, and methylation, a control system, like a computer access control system, or an encryption system, acts like a control process that determines whether or not certain programs are made available or not. This is also essential to the fact that very different cell types have the same DNA at the fundamental level.
4. The hard-drives are protected by a redundancy and error correction system, analogous to RAID storage systems, that guarantee the autocorrection of glitches in data storage system, by maintaining at least two copies of each piece of information, together to validation and error detection keys (Like parity and CRC checks) that will identify an error and hence the system will seek to correct it! DNA damage repair mechanisms work with the double strands of the DNA to perform this function, apart from more sophisticated systems that relate to the so-called “non-coding” regions of the DNA.
5. Nuclear pores, a security system that protects the data center, the nucleus, like an anti-virus or a firewall, secures that the right programs get executed if they are really needed, and that hackers will have less chances to run unauthorized programs or corrupt the system software.
6. The DNA transcription process is analogous to reading the instructions stored on the DNA, and loading it into memory, where RNA is like a program.
7. The program loaded into memory, may need to be pre-processed prior to being executed, analogous to being compiled into executable code, and this is what the excision and ligation process does!
8. The RNA code translation is now analogues to executing the program in memory, producing the required protein.
9. Now, proteins are typically not directly useable, but they need to be folded into its useful shape, analogous to a rendering process of a 3-D graphic that needs to be displayed on the computer screen, or controlling an external device to print a certain 3-D shape through a 3D printer! Enzymes, like molecular chaperones. Those are themselves proteins that needed to be transcribed-translated at a prior stage to close the loop.
10. Now, the produced protein will need to be transported to where it will be rendered useful to perform its function, but this is another story, which we addressed partially in the motor proteins discussion (review here).

It should be obvious enough by now, that the above process, which is only the tip of the ice-berg could never be the outcome of a process that has “evolved” through chance (mutation) and blind selection (Natural selection), as the existence of “natural” selection itself is a function in the existence of the genetic material that drives life in the first place, and mutation, a random process can not produce such a hyper-sophisticated process, with obvious specified complexity where parts are interaction in a predetermined pattern, where a misplaced part of process will lead to failure of the whole system.

Chromosome: The Hard Drives!

This video shows the wrapping of DNA into chromatin into chromosomes: https://youtu.be/gbSIBhFwQ4s

Replication!

This video shows the process of gene replication in preparation for division, the simplified version: https://youtu.be/6j8CV3droDw

This is a more involved version of the same process, zoomed in: https://youtu.be/I9ArIJWYZHI

This one is in a graphics format, and goes into more details concerning the three phases of the process, and gives more details concerning the leading and lagging strands: https://youtu.be/0Ha9nppnwOc

Epigenetics: Access control!

This video shows a rendering at the molecular level of the helix, the histones, and acetylation opening access to the genetic material: https://youtu.be/4Z4KwuUfh0A

This video shows the process of gene silencing by a methyl group: https://youtu.be/29doT6Hf2MI

DNA Damage repair: Error Identification and correction:

This video gives a high-level overview of some of what damage repair mechanisms can do: https://youtu.be/2yI_SoOWFMU?t=15

This video gives an insight into what happens on the molecular level to prepare some of the molecular machines that actually execute the repair processes seen above: https://youtu.be/ceFr0xTMV5k

Nuclear Pores: The firewall!

The nuclear pore is a protein-lined channel in the nuclear envelope that regulates the transportation of molecules between the nucleus and the cytoplasm. In eukaryotic cells, the nucleus is separated from the cytoplasm and surrounded by a nuclear envelope. This envelope safeguards the DNA contained in the nucleus. In spite of this barrier, there is still communication between the nucleus and the cytoplasm. This communication is regulated by the nuclear pores.

Each nuclear pore is a large complex of proteins that allows small molecules and ions to freely pass, or diffuse, into or out of the nucleus. Nuclear pores also allow necessary proteins to enter the nucleus from the cytoplasm if the proteins have special sequences that indicate they belong in the nucleus. These sequence tags are known as nuclear localization signals. Similarly, RNA transcribed in the nucleus and proteins that are destined to enter the cytoplasm have nuclear export sequences that tag them for release through the nuclear pores.

This video shows exporting of proteins from the nucleus: https://youtu.be/9v-13EZWVk8

This video shows import into the nucleus: https://youtu.be/UyhqLpjicZg

DNA Transcription: Loading into Memory!

DNA stores genetic information, but to be executed, the information needs to be read into an executable form, just like a computer program stored on a hard drive would be loaded into memory prior to execution. Obviously the technology used for long term storage on a hard-drive is typically not the same as that of the computer memory, where the code is more accessible, and can read to produce executable instructions that render results. The substance that carries the executable genetic information is called RNA. RNA is typically a single stand of genetic material (though there is double stranded RNA), and can be then transcribed into proteins (which are the machinery that will do the actual work. In many cases, RNA itself is a useful machine and can be directly used or gets combined with other proteins and/or RNA’s to form larger machine complexes.

What initiates the transcription? (Regulation)

6.0. This video gives a glance over how the cell knows a production of a protein is needed in the first place, how process initiates a cascade of events, and how the necessary components are prepared outside the nucleus and then into the cell, to eventually fit in their places and initiate the process as demanded: https://youtu.be/vi-zWoobt_Q

6.0.1. This video sheds a light over how the transcription factors find the correct DNA sequences to find the genes that they should transcribe, and the specific promoter zone that they bind to along the DNA strand! This process is so amazingly intricate as it shows the transcription factor scanning the strand, hopping over obstacles, and even jumping between strands like a gymnast: https://youtu.be/MkUgkDLp2iE

A look at the overall process

This video shows the magnificent process of Transcription of DNA into RNA then protein – simplified: https://youtu.be/gG7uCskUOrA

Focus on Transcription Initiation process

This video focuses on the process of transcription initiation and then the transcription – medium: https://youtu.be/SMtWvDbfHLo

Focus on Transcription Complex

This video focuses more on the intricacies of the assembly of the Transcription Complex and the release of RNA Polymerase to start the transcription process: https://youtu.be/JtwMBD7tSGg

You can find more information about the promoter region TATA box here: TATA box | Learn Science at Scitable (nature.com)

Focus on the RNA Polymerase complexity

This video shows the molecular structure of RNA Polymerase and its intricacy, which is in itself a product of DNA transcription, since it has RNA sub-units: https://youtu.be/GdKfadJGId4

This is what happens inside the RNA Polymerase to produce the RNA strand!

Lets watch the video and ask ourselves whether it is at all possible to have such an intricate process to occur by “Random” mutation: https://youtu.be/XzVXhemtwmA

Splicing: Compiling the program!

Programs in memory get to be compiled before execution; the processes of excision, or splicing are analogous (as far as we understand!!)!

7.0. First, the RNA is “prepared” for “processing”, by properly capping it at both sides: This is an overview of the process: https://youtu.be/YjWuVrzvZYA

7.1. This video shows the magnificent process of splicing that follows the processing: https://youtu.be/aVgwr0QpYNE

Translation of RNA

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To be continued with the next upcoming livestream! … stay tuned!

Ahmed Eshrah

Finding Truth