Wednesday, February 16, 2022

The Doll As Metaphor - 4

Proton induced RNA mutation

I. Background

I have tried to stimulate biologists/virologists into taking a look at the haphazard way RNA is depicted in major government databases (such as GenBank) to no avail (It's In The GenBank, 2, 3).

In the previous post of this series I set forth a wee bit of criticism based upon, among other things, the revolutionary work of Per-Olov Löwdin (see The Doll As Metaphor - 3).

In Löwdin's work he pointed out an abiological set of events, involving proton tunneling, that would engender mutations in microbe and virus genomes.

Long time Dredd Blog readers will remember that I also wrote about it several years ago (The Uncertain Gene; cf. If Cosmology Is "Off," How Can Biology Be "On?").

II. Proton Tunneling in DNA and its Biological Implications

Since Löwdin's hypothesis, others have addressed the subject (see eg. The Role of Proton Transfer on Mutations, An Open Quantum Systems approach to proton tunnelling in DNA, Comment on Masanari Asano et al.: A model of epigenetic evolution based on theory of open quantum systems).

Löwdin's concept is a revolutionary challenge to biologists, microbiologists, and virologists who want to play with their metaphorical dolls (microbes, viruses) by play pretending that they can do 'whatever evolution' (The Doll As Metaphor, 2, 3).

III. Proton Tunneling in RNA and its Biological Implications

So, let's take a look at the concept and specifically apply it to RNA rather than to DNA.

One of the papers took a deeper dive into the issue by addressing "where the rubber meets the road":

"One of the most important topics in molecular biology is the genetic stability of DNA. One threat to this stability is proton transfer along the hydrogen bonds of DNA that could lead to tautomerisation, hence creating point mutations. We present a theoretical analysis of the hydrogen bonds between the Guanine-Cytosine (G-C) nucleotide, which includes an accurate model of the structure of the base pairs, the quantum dynamics of the hydrogen bond proton, and the influence of the decoherent and dissipative cellular environment. We determine that the quantum tunnelling contribution to the process is several orders of magnitude larger than the contribution from classical over-the-barrier hopping. Due to this significant quantum contribution, we find that the canonical and tautomeric forms of G-C inter-convert over timescales far shorter than biological ones and hence thermal equilibrium is rapidly reached. Furthermore, we find a large tautomeric occupation probability of 1.73 × 10 −4 , suggesting that such proton transfer may well play a far more important role in DNA mutation than has hitherto been suggested. Our results could have far-reaching consequences for current models of genetic mutations."

(An Open Quantum Systems approach to proton tunneling in DNA, Cornell University, September 2021, emphasis added). This more recent Cornell University work is where I begin.

That Cornell University Paper uses the A-T ('T' = thymine) base pair of DNA in its work, whereas I will use the A-U ('U' = uracil) base pair of RNA in this post:

"Uracil is a pyrimidine type nitrogenous base that is found only in RNA molecules. It always pairs with adenine. Chemical difference of uracil and thymine is very small. Uracil has a hydrogen atom at C-5 carbon while thymine has a methyl group at the same [C-5]carbon."

(Difference Between Thymine and Uracil). My hypothesis is that the proton tunneling is less complicated in a single entity ("hydrogen atom") location than it is at "a methyl group" location (Uracil has a surprising new kind of proton transfer; cf. The Role of Reaction Force and Chemical Potential in Characterizing the Mechanism of Double Proton Transfer in the Adenine-Uracil Complex).

Furthermore, RNA mutation rates are orders of magnitude greater than DNA mutation, suggesting a closer look and further exploration is needed.

IV. Closing Comments

Thus, the Cornell University Paper's "probability of 1.73 × 10 −4" of proton tunneling at the A-T location in DNA is less probable than the even more likely probability at the A-U location in RNA.

In a future post I will "do the math", so stay tuned as we try to figure it out:

"Last January, a team of researchers searching for the coronavirus in New York City’s wastewater spotted something strange in their samples. The viral fragments they found had a unique constellation of mutations that had never been reported before in human patients — a potential sign of a new, previously undetected variant [a.k.a. dead bodies of microbes and viruses] ... because wastewater samples contain an amalgamation of lineages circulating in the sewer-shed, it is not possible to reconstruct individual genomes using standard methods."

(Mysto SARS-CoV-2 in NY , p. 2). We don't have much time before Halloween.

The next post in this series is here, the previous post in this series is here.

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