Direct evidence for dark DNA?!

This morning I learned in Sciencedaily about extremely interesting finding related to DNA. The finding is just what breakthrough discovery should be: it must be something impossible in the existing world view.

What has been found is that knock-out (removing parts of gene to prevent transcription to mRNA) and knock-down of gene (prevent protein translation) seem to have different consequences. Removing parts of gene need not have the expected effect at the level of proteins! Does this mean that somehow DNA as a whole can compensate the effects caused by knock-out but not those by knock-down?

Could this be explained by assuming that genome is a hologram as Gariaev et al have first suggested? Also TGD leads to a vision about living system as a conscious hologram. Small local changes of genes could be compensated. Somehow the entire genome would react like brain to a local brain damage: other regions of brain take the duties of the damaged region.

Could the idea about DNA double strand as nano-brain having left and right strands instead of hemispheres help here. Does DNA indeed act as a macroscopic quantum unit? The problem is that transcription is local rather than holistic process. Something very simple should lurk behind the compensation mechanism.

Could transcription transform dark DNA to dark mRNA?

Also the TGD based notion of dark DNA comes in mind (see this and this). Dark DNA consists of dark proton sequences for which states of single DNA proton correspond to those of DNA, mRNA, aminoacids, and tRNA. Dark DNA is one of the speculative ideas of TGD inspired quantum biology getting support from Pollack's findings . Ordinary biomolecules would only make their dark counterparts visible: dark biomolecules would serve as a template around which ordinary biomolecules such as DNA strands are formed in TGD Universe.

Although ordinary DNA is knocked out of ordinary gene, dark gene would still exist! If dark DNA actually serves as template for the transcription to mRNA, everything is still ok after knockout! Could it be that we do not understand even transcription correctly? Could it actually occur at the level of dark DNA and mRNA?! Dark mRNA would attach to dark DNA after which ordinary mRNA would attach to the dark mRNA. One step more!

Damaged DNA could still do its job! DNA transcription would would have very little to do with bio-chemistry! If this view about DNA transcription is correct, it would suggest a totally new manner to fix DNA damages. These damages could be actually at the level of dark DNA, and the challenge of dark genetic engineering would be to modify dark DNA to achieve a proper functioning.

Could dark genetics help to understand the non-uniqueness of the genetic code?

Also translation could be based on pairing of dark mRNA and dark tRNA. This suggests a fresh perspective to some strange and even ugly looking features of the genetic code. Are DNA and mRNA always paired with their dark variants? Do also amino-acids and anticodons of tRNA pair in this manner with their dark variants? Could the pairings at dark matter level be universal and determined by the pairing of dark amino-acids with the anticodons of dark RNA? Could the anomalies of the code be reduced to the non-uniqueness of the pairing of dark and ordinary variants of basic bio-molecules (pairings RNA--dark RNA, amino-acid-- dark amino-acid, and amino-acid--ordinary amino-acid in tRNA).

1. There are several variants of the genetic code differing slightly from each other: correspondence between DNA/mRNA codons and amino-acids is not always the same. Could dark-dark pairings be universal? Could the variations in dark anticodon - anticodon pairing and dark amino-acid-amino-acid pairing in tRNA molecules explain the variations of the genetic code?
   
   
2. For some variants of the genetic code a stop codon can code for amino-acid. The explanation at the level of tRNA seems to be the same as in standard framework. For the standard code the stop codons do not have tRNA representatives. If stop codon codes for amino-acids, the stop codon has tRNA representation. But how the mRNA knows that the stop codon is indeed stop codon if the tRNA associated with it is present in the same cell?
   

   Could it be that stop codon property is determined already at the level of DNA and mRNA? If the dark variant of genuine stop codon is missing in DNA and therefore also in mRNA the translation stops if it is induced from that at the level of dark mRNA. Could also the splicing of mRNA be due to the splitting of dark DNA and dark mRNA? If so genes would be separated from intronic portions of DNA in that they would pair with dark DNA. Could it be that the intronic regions do not pair with their dark counterparts. They would be specialized to topological quantum computations in the TGD inspired proposal.
   

   Start codon (usually AUG coding met) serves as a start codon defining the reading frame (there are 3 possible reading frames). Dark DNA would naturally begin from this codon.
   
   

3. Also two additional amino-acids Pyl and Sec appear in Nature. Gariaev et al have proposed that the genetic code is context dependent so that the meaning of DNA codon is not always the same. This non-universality could be reduced to the non-uniqueness of dark amino-acid--amino-acid pairing in tRNA if genetic code is universal.

Could dark genetics help to understand wobble base pairing?

Wobble base pairing is second not-so-well understood phenomenon. In the standard variant of the code there are 61 mRNAs translated to amino-acids. The number of tRNA anticodons (formed by the pairs of amino-acid and RNA molecules) should be also 61 in order to have 1-1 pairing between tRNA and mRNA. The number of ordinary tRNAs is however smaller than 61 in the sense that the number of RNAs associated with them is smaller than 45. tRNA anticodons must be able to pair with several mRNA codons coding for given amino-acid. This is possible since tRNA anticodons can be chosen to be representative for the mRNA codons coding a given amino-acid in such that all mRNA codons coding for the same amino-acid pair with at least one tRNA anticodon.

1. This looks somewhat confusing but is actually very simple: genetic code can be seen as a composite of two codes: first 64 DNAs/mRNAs to are coded to N<45 anticodons in tRNA, and then these N anticodons are coded to 20 amino-acids. One must select N anticodon representatives for the mRNAs in the 20 sets of mRNA codons coding for a given amino-acid such that each amino-acid has at least one anticodon representative. A large number of choices is possible and the wobble hypothesis of Crick pose reduce the number of options.
   
   
2. The wobble hypothesis of Crick states that the nucleotide in the third codon position of RNA codon of tRNA has the needed non-unique base pairing: this is clear from the high symmetries of the third basis. There is exact U-C symmetry and approximate A-G symmetry with respect to the third basis of RNA codon (note that the conjugates of RNA codons are obtained by A↔U and C↔G permutations).
   
   
3. The first two basis in the codon pair in 1-1 manner to the second and third basis of anticodon. The third basis of anticodon corresponds to the third letter of mRNA codon. If it is A or C the correspondence is assumed to be 1-to-1: this gives 32 tRNAs. If the first basis of anticodon is G or U the 2 mRNA basis can pair with it: they would be naturally A for G and C for U by symmetry. One would select A from A-G doublet and C from U-C double. This would give 16 anticodons: 48 anticodons altogether, which is however larger than 45. Furthermore, this would not give quite the correct code since A-G symmetry is not exact.
   

   Smaller number of tRNAs is however enough since the code has almost symmetry also with respect to A and C exchange not yet utilized. The trick is to replace in some cases the first basis of anticodon with Inosine I, which pairs with 3 mRNA basis. This replacement is possible only for those amino-acids for which the number of RNAs coding the amino-acid is 3 or larger (the amino-acids coded by 4 or 6 codons).
   
   

4. It can be shown at least 32 different tRNAs are needed to realize genetic code by using wobble base pairing. Full A-C and G-U symmetry for the third basis of codon would give 16+16=32 codons. Could one think that tRNA somehow realizes this full symmetry?
   
   

How dark variants of could help to understand wobble base pairing? Suppose for a moment that the visible genetics be a shadow of the dark one and fails to represent it completely. Suppose the pairing of ordinary and dark variants of tRNA anticodons resp. amino-acids and that translation proceeds at the level of dark mRNA, dark anticodons, and dark amino-acids, and is made visible by its bio-chemical shadow. Could this allow to gain insights about wobble base pairing? Could the peculiarities of tRNA serve for some other - essentially bio-chemical - purposes?

The basic idea would be simple: chemistry does not determine the pairing but it occurs at the level of the dark mRNA codons and dark tRNA anticodons. There would be no need to reduce wobble phenomenon to biochemistry and the only assumption needed would be that chemistry does not prevent the natural dark pairing producing standard genetic code apart from the modifications implied by non-standard dark amino-acid--amino-acid pairing explaining for different codes and the possibility that stop codon can in some situation pair with dark mRNA.

One can consider two options.

1. The number of dark tRNAs is 64 and the pairings between dark mRNA and dark anticodons and dark anticodons and dark amino-acids are 1-to-1 and only the pairing between dark RNA codons and anticodons in tRNA is many-to-1.
   
   
2. The model of dark genetic code) suggests that there are 40 dark proton states, which could serve as dark analogs of tRNA. This number is larger than 32 needed to realize the genetic code as a composite code. I have cautiously suggested that the proposed universal code could map dark mRNA states of the same total spin (there is breaking of rotational symmetry to that around the axis of dark proton sequences) to dark tRNA/dark amino-acid states with the same total spin. The geometric realization would in terms of color flux tubes connecting the dark protons of corresponding dark proton sequences. Also in ordinary nuclei nucleons are proposed to be connected by color flux tubes so that they form nuclear strings and dark proton sequences would be essentially dark variants of nuclei.
   

One should understand the details of the dark mRNA--tRNA anticodon correspondence. One can also ask whether the dark genetic code and the code deduced from the geometric model for music harmony in terms of Platonic solids are mutually consistent. This model implies the decomposition of 60+4 DNA codons to 20+20+20+4 codons, where each "20" corresponds to one particular icosahedral Hamilton's cycle with characteristic icosahedral symmetries. "4" can be assigned to tetrahedron regarded either disjoint from icosahedron or glued to it along one of its faces. This allows to understand both the standard code and the code with two stop codons in which exotic amino-acids Pyl and Sec appear. One should understand the compositeness 64→ 40\→20 of the dark genetic code and and whether it relates to the icosatetrahedral realization of the code.

I have proposed that dark variants of transcription, translation, etc.. can occur and make possible kind of R&D laboratory so that organisms can test the consequences of variations of DNA. If ordinary translation and transcription are induced from their dark variants and if dark biomolecules could also appear as unpaired variants, these processes could occur as purely dark variants. Organisms could indeed do experimentation in the virtual world model of biology and pairing with ordinary bio-molecules would make things real.

For background see the chapter Quantum Gravity, Dark Matter, and Prebiotic Evolution.

For a summary of earlier postings see Links to the latest progress in TGD.