Saturday, June 02, 2018

Replication of sequences of RNA codons is possible also in presence of folding!

There was a very interesting popular article in Spacedaily with title "Scientists crack how primordial life on Earth might have replicated itself" (see this). The research paper "Ribozyme-catalysed RNA synthesis using triplet building blocks" is here.

It is possible to replicate unfolded RNA strands in Lab by using enzymes known as ribozymes, which are RNA counterparts of enzymes, which are amino-adic sequences. In the presence of folding the replication is however impossible. Since ribozymes are in general folded, they cannot catalyze their own replication in this manner. The researchers however discovered that the replication using RNA triplets - genetic codons - as basic unit can be carried out in laboratory even for the folded RNA strands and with rather low error rate. Also the ribozyme involved can thus replicate. For units longer than 3 nucleotides the replication becomes prone to errors.

These findings are highly interesting in TGD framework. In TGD chemical realization of genetic code is not fundamental. Rather, dark matter level would provide the fundamental realizations of analogs of DNA, RNA, tRNA, and amino-acids as dark proton sequences giving rise to dark nuclei at magnetic flux tubes. Also ordinary nuclei correspond in TGD Universe to sequences of protons and neutrons forming string like entities assignable to magnetic flux tubes.

The basic unit representing DNA, RNA and tRNA codon and amino-acid would consist of 3 entangled dark protons. The essential aspect is that by entanglement the dark codons do not decompose to products of letters. This is like words of some languages, which do not allow decomposition to letters. This representation is holistic. As we learn to read and write, we learn the more analytic western view about words as letter sequences. Could the same hold true in evolution so that RNA triplets would have come first as entities pairing with dark RNA codons from from dark proton triplets as a whole? Later DNA codons would have emerged and paired with dark DNA codons. Now the coupling would have have been letter by letter in DNA replication and transcription to mRNA.

It is intriguing that tRNA consists of RNA triplets combined from amino-acids and analogs of mRNA triplets! The translation of mRNA to amino-acids having no 3-letter decomposition of course forces the holistic view but one can ask whether something deeper is involved. This might be the case. I have been wondering whether during RNA era RNA replicated using a prebiotic form of translational machinery, which replicated mRNA rather than translated RNA to protein formed from amino-acids (AAs).

  1. During RNA era amino-acids associated with pre-tRNA molecules would served as catalysts for replication of RNA codons. The linguistic mode would have been "holistic" during RNA er in accordance with the findings of the above experiments. RNA codon would have been the basic unit.

  2. This would have led to a smaller number of RNAs since RNA and RNA like molecules in tRNA are not in 1-1 correspondence. A more realistic option could have been replication of subset of RNA molecules appearing in tRNA in this manner.

  3. Then a great evolutionary leap leading from RNA era to DNA era would have occurred. AA catalyzed replication of RNA would have transformed to a translation of RNA to proteins and the roles of RNA and AA in tRNA would have changed. [Perhaps the increase of heff in some relevant structure as quantum criticality was reached led to the revolution?]

  4. At this step also (subset of) DNA and its transcription to (a subset of) mRNA corresponding to tRNA had to emerge to produce mRNA in transcription. In the recent biology DNA replicates and is transcribed nucleotide by nucleotide rather than using codon as a unit so that DNA and RNA polymerases catalyzing replication and transcription should have emerged at this step. An alternative option would involve the "tDNA" as the analog of "tRNA" and the emergence of polymerases later: this does not however look attractive if one accepts the idea about the transition from holistic to analytic mood.

    The ability of DNA to unwind is essential for the emergence of the "analytic linguistic mode" as an analog of written language (DNA) decomposing codons to triplets of letters. This must have been a crucial step in evolution comparable to the emergence of written language based on letters. Also the counterpart of RNA polymerase and separate RNA nucleotides for transcription should have emerged if not already present.

    The minimal picture would be emergence of a subset of DNA codons corresponding to RNAs associated with pre-tRNA and the emergence of the analogs of DNA and RNA polymerases as the roles of amino-acid and RNA codon in tRNA were changed.

  5. How DNA could have emerged from RNA? The chemical change would have been essentially the replacement of ribose with de-oxiribose to get DNA from RNA and U→ T. Single O-H in ribose was replaced with H. O forms hydrogen bonds with water and this had to change the hydrogen bonding characteristics of RNA.

    If the change of heff =n×h0 (one has h= 6× h0 in the most plausible scenario, see this and this) was involved, could it have led to stabilization of DNA. Did cell membrane emerge and allow to achieve this? I have proposed (see this) that the emergence of cell membrane meant the emergence of new representation of dark genetic code based on dark nuclei with larger value of heff.

The communication between dark and ordinary variants of biomolecules involves resonance mechanism and would also involve genetic code represented as 3-chords, music of light, and it is interesting to see whether this model provides additional insights.
  1. The proposal is that 3-chords assignable to nucleotides as music of light with allowed 64 chords defining what I have called bio-harmony is essential for the resonance (see this, this, and this). The 3 frequencies must be identical in the resonance: this is like turning 3 knobs in radio. This 3-fold resonance would correspond to the analytic mode. The second mode could be holistic in the sense that it would involve only the sum only the sum of the 3 frequencies modulo octave equivalence assigning a melody to a sequence of 3-chords.

  2. The proposal is that amino-acids having not triplet decomposition are holistic and couple to the sum of 3 frequencies assignable to tRNA and mRNA in this manner. Also the RNAs in tRNA could couple to mRNA in this manner. One could perhaps say that tRNA, mRNA and amino-acids codons sing whereas DNA provides the accompaniment proceeding as 3-chords. The couplings of DNA nucleotides to RNA nucleotides would realy on the frequencies assignable to nucleotides.

  3. If the sum of any 3 frequencies associated with mRNA codons is not the same except when the codons code for the same amino-acids, the representation of 3-chords with the sum of the notes is faithful. The frequencies to DNA and RNA nucleotides cannot be however independent of codons since the codons differing only by a permutation of letters would correspond to the same frequency and therefore code for the same amino-acid. Hence the information about the entire codon would be needed also in transcription and translation and could be provided either by dark DNA strand associated with DNA strand or by the interactions between the nucleotides of the DNA codon.

  4. The DNA codon itself would know that if is associated with dark codon and the frequencies assignable to nucleotides are determined by the dark DNA codon. It would be enough that the frequency of the letter depends on its position in the codon so that there would be 3 frequencies for every letter: 12 frequencies altogether.

    What puts bells ringing is that this the number of notes in 12-note scale for which the model of bio-harmony (see this and this) based on the fusion of icosahedral (12 vertices and 20 triangular faces) and tetrahedral geometries by gluing icosahedron and tetrahedron along one face, provides a model as Hamiltonian cycle and produces genetic code as a by-product. Different Hamiltonian cycles define different harmonies identified as correlates for molecular moods.

    Does each DNA nucleotide respond to 3 different frequencies coding for its position in the codon and do the 4 nucleotides give rise to the 12 notes of 12-note scale? There are many choices for the triplets but a good guess is that the intervals between the notes of triplet are same and that fourth note added to the triplet would be the first one to realize octave equivalence. This gives uniquely CEG #, C#FA,DF#/B b, and DG#B as the triplets assignable to the nucleotides. The emergence of 12-note scale in this manner would be a new element in the model of bio-harmony.

    There are 4!=24 options for the correspondence between {A, T, C, G} as the first letter and {C,C#,D,D#}. One can reduce this number by a simple argument.

    1. Letters and their conjugates form pyrimidine-purine pairs T, A and C,G. The square of conjugation is identity transformation. The replacement of note with note defining at distance of half-octave satisfies this condition (half-octave - tritonus - was a cursed interval in ancient music and the sound of ambulance realizes it).
      Conjugation could correspond to a transformation of 3-chords defined as

      CEG# ↔ DF#Bb , C#FA↔ D#GB .

    2. One could have

      {T, C} ↔ {CEG #, C#FA} , {A,G}↔ {DF#Bb,D#GB}

      or

      {T, C} ↔ {DF#Bb,D#GB} , {A,G}↔ {CEG#, C#FA} .

    3. One can permute T and C and A and G in these correspondences. This leaves 8 alternative options. Fixing the order of the image of (T, C) to say (C,C#) fixes the order of the image of (A, G) to (D,D#) by the half-octave conjugation. This leaves 4 choices. Given the bio-harmony and having chosen one of these 4 options one could therefore check what given DNA sequence sounds as a sequence of 3-chords (see this).

      Anyone willing to do this kind of experimentation obtains from me the program modules used the Garage band programs to produce a sequence of chords. A further interesting experiment would be check what kind of melodies come out if one assigns to a chord a note as the sum of frequencies of the chord reduced by octave equivalence to basic octave.

    That the position the frequency associated with the nucleotide depends on its position in the codon would also reflect the biochemistry of the codon and this kind of dependence would be natural. In particular, different frequencies associated with the first and third codon would reflect the parity breaking defining orientation for DNA.

For a summary of earlier postings see Latest progress in TGD.

Articles and other material related to TGD.

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