Article 3: LUCA’s Paradox: DNA, RNA, Proteins, and Enzymes

What is LUCA?

According to the theory of evolution, LUCA, the (Last Universal Common Ancestor), is the ancestor to which every creature that lives today traces back to, and the tree of life branches from there with continuous modification by Random Mutations and Natural selection.
Can we verify this by science and reason?
I am posting seven paradoxes pertaining to the question of LUCA.

So, let’s explore the question!

DNA is the core of self-replication

It is a fact that every living organism on the face of the earth, that is self-replicating, has DNA at its core, despite the relentless search by scientist for life that is self replicating based on RNA, with no positive results! (Paper: looking for DNA-less life: https://pubmed.ncbi.nlm.nih.gov/22093146/). (Note: viruses, including RNA viruses in this context, are not considered living organisms by mainstream science, and in all cases they need hosts to replicate).

Error Correction

Now, we have seen in a previous episode how living cells protect their DNA replication process, so that extremely few errors occur, through having a cascade of error detection and correction mechanisms. Error rates of DNA replication after error correction are as low as 1 in a billion (10^9) to 1 in a hundred billion (10^11)! (Read about Replication fidelity in ecoli: https://pubmed.ncbi.nlm.nih.gov/22404288/ ).
We’ve also seen living cells applying monitoring systems to find and repair damage in DNA during the cell life-cycle. Damage in a typical cell per day can go up to 10 thousand – 1 million letters per day (nucleotides), most of which get repaired by the cell via various mechanisms (Check this wiki under DNA damage: “DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 10,000 to 1,000,000 molecular lesions per cell per day”: https://en.wikipedia.org/wiki/DNA_repair , reference embedded: Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J (2004). Molecular Biology of the Cell (5th ed.). New York: WH Freeman. p. 963.).
Even damage induced by viral infections to cellular DNA can trigger DNA repair mechanisms to fight back against the virus. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808796/ )
Defense against DNA damage can go to the length that if the damage is too big to fix, the cell can commit suicide (initiate intrinsic apoptosis pathway: video Apoptosis Intrinsic pathway: https://youtu.be/DR80Huxp4y8?t=163) to prevent replication of the distorted DNA; which happens, for example, in the case of virus induced DNA damage. (Check item number 8 in this interesting Nature paper about Activation of the DNA Damage Response by RNA Viruses: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808796/ )
Some are even arguing that DNA genomes have an underlying error correction system in its very coding system, considering Introns and Exons, in an algorithmic manner (it is very exciting to follow this research to see what it might bring to the table)!! (Read: Is a Genome a Codeword of an Error-Correcting Code? https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036644)
Surprise: All DNA-based life (that we know of) has error correction, including prokaryotes! ( Note the quote ” All cells possess DNA-repair enzymes” in chapter 14 here: https://www.ncbi.nlm.nih.gov/books/NBK21114/ , and Check item number 3 under Single Strand damage: https://en.wikipedia.org/wiki/DNA_repair).

How did LUCA begin?

One wonders how such a super-sophisticated integrated system could have been available to living cells from the outset of life through blind chemical evolution, right after the alleged process of Abiogenesis (which is a topic of its own)! And obviously scientists wondered the same too, and hence, they conceded that if chemical evolution caused life to emerge on earth and produced the first protocell, then the cell would potentially have genetic material that is RNA based, not DNA, but why did they assume that, and what are the implications of all of this! (Read this light article about LUCA: https://www.imperial.ac.uk/news/120606/who-what-luca/ , and this one that considers looking for common genes and lateral gene transfer scenario: https://astrobiology.nasa.gov/news/looking-for-luca-the-last-universal-common-ancestor/ ).

On the other hand, this interesting 2018 article (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095482/) is more inclined that LUCA had DNA, but towards the end is hesitant about it and says under title (The onset of genetics):

Though the organization of inanimate matter into living cells with genetics can be charted in mathematical terms [120,121], the biochemical details remain elusive. For example, it is controversial whether LUCA had DNA or not [87]. Several DNA-binding proteins trace to LUCA [78], so it would appear that LUCA possessed DNA, but it is unresolved whether LUCA could actually replicate DNA. For LUCA, DNA might just have been a chemically stable repository for RNA-based replication [122].

So, it seems that at the end, even the advocates of a DNA LUCA still resort to RNA being primary in the picture, hence, in this discussion, I will take the following line of thought, until the conclusion, where it will not make a real difference:

1. LUCA was an RNA-based life form.
2. If the above article is correct (this one), then we can consider it to be equivalent to the above option, since DNA in their proposal does not have replication! Otherwise, we resort to option 3 below.
3. If the LUCA of modern day creatures (that we are using to trace back genetics), then our LUCA (according to RNA world hypothesis) needs to have an ancestor that is RNA based anyway, which we can ironically call the RNA LUCA of our LUCA. So, in the case our LUCA was DNA based, our discussion would be referring to the earlier LUCA.
4. If the RNA hypothesis is totally abandoned by the evolutionary community and they concede that there was no RNA life prior to a DNA LUCA, then the  theory remains in real trouble, because DNA as we know it cannot pop out of no where due to its utmost complexity. Already voices are speaking against the RNA world hypothesis, yet their proposals are incomplete and still not giving adequate answers to our questions in this article (read about peptide-RNA world or lipids world here: https://www.quantamagazine.org/the-end-of-the-rna-world-is-near-biochemists-argue-20171219/)

At the end of this article, I consider the various possibilities too, and all ends up to hit the paradox anyway, so, we are good to go!

Understanding RNA

Well, we need to understand more about what RNA is, and how different it is versus DNA to appreciate the issue, and hence to look into its implications concerning LUCA and the origin of species!
So, the first thing is the role of RNA in the genetic system, and what it does:
DNA is analogous to code on a hard-disk (read this very interesting article about this topic: An examination of the structure and function of computer hard drives and DNA https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829000/) , while RNA is like the program read into memory, and hence executed (some actually propose using it for biological programming! Read, Using RNA as Molecular Code for Programming Cellular Function: https://pubs.acs.org/doi/10.1021/acssynbio.5b00297 ). Finally, the protein and its consequences/actions is like the product of a program-run.
RNA carries genetic information, but it comes typically in one strand (not always two like DNA), and is less stable and prone to errors!
RNA, specifically mRNA, in brief, is used an intermediate phase between the DNA that hold the genetic code and the production of Proteins. RNA is synthetized by reading DNA by a molecular machine (video about the transcription process: https://youtu.be/gG7uCskUOrA ) which produces an RNA strand (premature mRNA). Because DNA has regions (called introns) that produces RNA that is not relevant to the Protein, it is then cleaved by another machine and then glued together to keep only mRNA, the process is called splicing (video about the wonderful process of splicing using spliceosomes: https://youtu.be/aVgwr0QpYNE ).

Enzymes

Messenger RNA (mRNA) is then translated into a protein using a molecular machine called the Ribosome, which is like a programmable 3D printer that reads the RNA and assembles the Protein it encodes. The protein is then properly folded and modified by other enzymes to be ready to perform its function (This video illustrates protein folding: https://youtu.be/yZ2aY5lxEGE ).
The produced protein can be itself an enzyme. Enzymes are essential for the execution of chemical reactions in the cell, including the processes of replication, transcription, and translation, which are led by enzymes already! (watch this video about the role of enzymes in catalyzing reactions and other roles: https://youtu.be/yk14dOOvwMk).
Without Enzymes, nothing would happen in the cell! An enzyme will make a reaction occur up to 1 trillion times its speed in the absence of the enzyme. (Ref: see above)
Enzymes are hence the motor of life’s reactions, and it is the product of the transcription and translation processes that are themselves processed by enzymes! It poses the question: which came first, the enzymes or the DNA itself, because they need to be both there for life to proceed.

DNA-based life even posses mechanisms to apply “Quality Control” to mRNA and its products, using enzymes, and there are speculations that it goes the length to mRNA repair (in the cases where it is at all possible) instead of degradation (note that RNA lacks the matching strand that can be used as a template for repair)!! Yet, such mechanisms obviously depend on machinery that is itself generated from DNA-based genes found in DNA-based life, including the Ribosome itself, the primary machine that processes mRNA for production of proteins (Read, How do cells cope with RNA damage and its consequences?: https://www.jbc.org/article/S0021-9258(20)34972-3/fulltext ).

LUCA, is it RNA with or without error correction?

Yet, as usual, with evolutionary theorists, they use the above research that is pertinent to DNA-based life, such that some would like to use it to speculate that if LUCA was to survive, as an RNA-based cell, then it should have had RNA error correction. (You can read about this speculation here: https://www.researchgate.net/publication/7961336_Modern_mRNA_Proofreading_and_Repair_Clues_that_the_Last_Universal_Common_Ancestor_Possessed_an_RNA_Genome ). Yet, in the abstract, I quote: “There are significant gaps in our understanding of how the modern protein-DNA world could have evolved from a simpler system, and it is currently uncertain whether DNA genomes evolved once or twice.”, which is an important confession, not properly publicized, as usual, in the media of biased science journalism.
Even though DNA polymerases have proofreading abilities, they still make mistakes – on the order of about one misincorporation per 10^7 to 10^9 nucleotides polymerized. But the RNA polymerases of RNA viruses are the kings of errors – these enzymes screw up as often as one time for every 1,000 – 100,000 nucleotides polymerized. ( https://www.virology.ws/2009/05/10/the-error-prone-ways-of-rna-synthesis/ and https://www.nature.com/scitable/topicpage/dna-replication-and-causes-of-mutation-409/).
RNA viruses have high mutation rates—up to a million times higher than their hosts ( https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000003 ).

RNA Viruses cannot self replicate!

It is worth noting to say that viruses, of which are RNA-based viruses, cannot self-replicate outside of a living cell, and would depend on a host to replicate themselves! So, the message is: no DNA in the cell, no reproduction, and no independent life! (Note about RdRp “RNA-dependent RNA polymerase”: https://en.wikipedia.org/wiki/RNA-dependent_RNA_polymerase ).

While some viruses can replicate their genetic material without having to hijack cellular DNA ( Self-replicating viruses: https://pubmed.ncbi.nlm.nih.gov/30551668/ ), they still cannot do the replication outside the cytoplasm of a DNA-based cell. So, the one quasi-life form that we know about, which is centered around RNA, cannot proceed into its life-cycle without an existing DNA-based environment!

The Seven Paradoxes

The following questions will still apply, even if LUCA was a DNA-based cell, because we will again have to ask how we arrived to a DNA-based cell from its ancestral RNA based primordial life.

Session critical questions:

1. How was it possible for RNA-based life to survive and stabilize to become the root of the tree of life, given the obvious instability and vulnerability of RNA and absence of error correction mechanisms?!

2. How come, if LUCA was an independently living RNA-based life, the only available RNA-based organisms, (RNA viruses), cannot lead an independent life, and can only replicate in the context of a host.

3. And if those error correction mechanisms came about by evolution, then how come after billions of years of evolution, from LUCA till the present day, How come viruses (till today) do not even have the error correction abilities that can protect them from attenuation due to excessive mutation like DNA based life?

4. If LUCA was RNA based, it means that RNA-based life was robust enough to stabilize and survive to the extent of taking a long evolutionary path to evolve into DNA based life. Since the development of a new clad does not entail the extinction of the ancestor, (for example, the evolution of humans from a chimp-like ancestor did not entail the discontinuation of the chimp form), THEN: Where are the self-replicating independent lifeforms that are still RNA based? Why is there none? Why is life today exclusively DNA based?

5. DNA needs enzymes to be replicated and transcribed, but the enzymes themselves need DNA to be produced!! So, if indeed DNA life emerged from RNA life, which has emerged first and how? The enzymes or the DNA?!

6. If we assume that DNA-based life emerged by chance through mutation, and in the outset in the absence of error correction mechanisms, then how did it survive until it “evolved” error correction mechanisms?! Is it possible to evolve error correction through the accumulation of mutational errors in the first place?

7. Likewise, if we stretch our imagination and assume DNA-based life came gradually, and in the absence of error correction it somehow became robust enough to survive long enough until error correction evolved, then where are those clads that are DNA-based living organisms without error correction?!! An obvious contradiction with the fact that all DNA-based life (that we know of) has error correction.

Those questions pose obvious contradictions to the assertions and the line of thought of the theory and a major challenging paradox to the assertion of LUCA as the ultimate common “Origin of species”!

It seems that LUCA is rather a paradox of the theory rather than a necessity!

The Chicken or the egg

So, is it the chicken or the egg that came first; except that this puzzle needs both simultaneously!
I leave you to consider those questions until the upcoming livestream.

Ahmed Abd ElSattar
Finding Truth

July 16th, 2021