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Genes and Memes

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Year 2016

Combinatorial Hierarchy: twenty years later

Combinatorial Hierarchy (CH) proposed by Noyes and Bastin is a hierarchy consisting of Mersenne integers M(n)= MM(n-1)=2M(n-1)-1 and starting from M1=2. The first members of the hierarchy are given by 2,3,7,127,M127=2127-1 and are primes. The conjecture of Catalan is that the hierarchy continues to some finite prime. It was proposed by Peter Noyes and Ted Bastin that the first levels of hierarchy up to M127 are important physically and correspond to various interactions (see this). I have proposed the levels of CH define a hierarchy of codes containing genetic code corresponding to M7 and also memetic code assignable to M127 (see this).

Pierre Noyes and Ted Bastin proposed also an argument why CH contains only the levels mentioned above. This has not been part of TGD view about CH: instead of this argument I have considered the possibility that CH does not extend beyond M127. With the inspiration coming from email discussion I tried to understand the argument stating that CH contains M127 as the highest level and ended up with a possible interpretation of the condition. Zero energy ontology (ZEO) and the representation of quantum Boolean statements A→ B as fermionic parts of positive and negative energy parts of zero energy states is essential. This led to several interesting new results.

  1. To my best understanding the original argument of Noyes and Bastin does not allow M127 level whereas prime property allows. States at M127 level cannot be mapped to zero energy states at M7 level. Allowing a wild association with Gödel's theorem, one could say that that there is hube number of truths at M127 level not realizable as theorems at M7 level.

    A possible interpretation is that M127 level corresponds to next level in the abstraction hierarchy defined by CH and to the transition from imbedding space level to the level of "world of classical worlds (WCW) in TGD. The possible non-existence of higher levels (perhaps implied if MM127 is not prime) could be perhaps interpreted by saying that there is no "world of WCWs"!

  2. Rather remarkably, for M7, which corresponds to genetic code (see this), the inequality serving as consistency condition is saturated. One can say that any set of 64 mutually consistent statements at M7 level can be represented in terms of 64 Boolean maps at M3 level representable in terms of zero energy states. One obtains an explicit identification for the Boolean algebras involved in terms of spin and isospin states of fermions in TGD framework at level M7 so that genetic code seems to be realized at the fundamental elementary particle level thanks to the dimension D=8 of imbedding space. Even more, the level M127 corresponding to memetic code emerges in the second quantization of fermions at M7 level. Here color triplet property of quarks and color singletness of leptons and the identification of elementary particles as pairs of wormhole contacts are in essential role.
The conclusion would be that in TGD Universe genetic code and its memetic counterpart are realized at the level of fundamental particles. Already earlier I have ended up with alternative realizations at the level of dark nucleons and sequences of 3 dark nucleons (see this).

For details see the chapter Genes and Memes or the article Combinatorial Hierarchy: two decades later.

Comparing TGD view about quantum biology with McFadden's views

McFadden has very original view about quantum biology: I have written about his work for the first time for years ago, much before the emergence of ZEO, of the recent view about self as generalized Zeno effect, and of the understanding the role of magnetic body containing dark matter (see this). The pleasant surprise was that I now understand McFadden's views much better from TGD viewpoint.

  1. McFadden sees decoherence as crucial in biological evolution: here TGD view is diametric opposite although decoherence is a basic phenomenon also in TGD.
  2. McFadden assumes quantum superpositions of different DNAs. To me this looks an unrealistic assumption in the framework of PEO. In ZEO it is quite possible option.
  3. McFadden emphasizes the importance of Zeno effect (in PEO). In TGD the ZEO variant of Zeno effect is central for TGD inspired theory of consciousness and quantum biology. Mc Fadden suggests that quantum effects and Zeno effect are central in bio-catalysis: the repeated measurement keeping reactants in the same position can lead to an increase of reaction rate by factors of order billion. McFadden describe enzymes as quantum mousetraps catching the reactants and forcing them to stay in same position. The above description for how catalysis catches the reactants using U-shaped flux tube conforms with mousetrap picture.

    McFadden discusses the action of enzymes in a nice manner and his view conforms with TGD view. In ZEO the system formed by catalyst plus reactants could be described as a negentropically entangled sub-self, and self indeed corresponds to a generalized Zeno effect. The reactions can proceed in shorter scales although the situation is fixed in longer scales (hierarchy of CDs): this would increase the length of the period of time during which reactions can proceed and lead to catalytic effect. Zeno effect in ZEO plus hierarchies of selves and CDs would be essentially for the local aspects of enzyme action.

  4. Protons associated with hydrogen bonds and electronic Cooper pairs play a universal role in McFadden's view and the localization of proton in quantum measurement of its position to hydrogen bond is the key step of enzyme catalysis. Also TGD dark protons at magnetic flux tubes giving rise to dark nuclear strings play a key role. For instance, McFadden models enzyme catalysis as injection of proton to a very special hydrogen bond of substrate. In TGD one has dark protons at magnetic flux tubes and their injection to a properly chosen hydrogen bond and transformation to ordinary proton is crucial for the catalysis. Typical places for reactions to occur are C=O type bonds, where the transition to C-OH can occur and would involve transformation of dark proton to ordinary proton. The transformation of dark proton to ordinary one or vice versa in hydrogen bonds would serve as a biological quantum switch allowing magnetic body to control biochemistry very effectively.

    What about electronic Cooper pairs assumed also by McFadden? They would flow along the flux tube pairs. Can Cooper pairs of electrons and dark protons reside at same flux tubes? In principle this is possible although I have considered the possibility that particles with different masses (cyclotron frequencies) reside at different flux tubes. For hgr =heff this would make possible both frequency and energy resonance for cyclotron transitions.

McFadden has proposed quantum superposition for ordinary codons: This does not seem to make sense in PEO since the chemistries of codons are different) but could make sense in ZEO. In TGD one could indeed imagine quantum entanglement (necessary negentropic in p-adic degrees of freedom) between dark codons. This NE could be either between additional degrees of freedom or between spin degrees of freedom determining the dark codons. In the latter case complete correlation between dark and ordinary DNA codons would imply also the superposition of their tensor products with ordinary codons.

The NE between dark codons could also have a useful function: it could determine physically gene as a union of disjoint mutually entangled portions of DNA. Genes are known to be highly dynamical units, and after pre-transcription splicing selects the portions of the transcript translated to protein. The codons in the complement of the real transcript are called introns and are spliced out from mRNA after the pre-transcription (see this).

What could be the physical criterion telling whether a given codon belongs to exonic or intronic portion of DNA? A possible criterion distinguish between exons and introns is that exons have NE between themselves and introns have no entanglement with exons (also exons could have NE between themselves). Introns would not be useless trash since the division into exonic and exonic region would be dynamical. The interpretation in terms of TGD inspired theory of consciousness is that exons correspond to single self.

An updated nuclear string variant is summarized and also its connection with the model of harmony is discussed in chapter Three new physics realizations of the genetic code and the role of dark matter in bio-systems and in the article About physical representations of genetic code in terms of dark nuclear strings.

Is bio-catalysis a shadow of dark bio-catalysis based on generalization of genetic code?

Protein catalysis and reaction pathways look extremely complex (see this) as compared to replication, transcription, translation, and DNA repair. Could simplicity emerge if biomolecules are identified as chemical shadows of objects formed from dark nuclear strings consisting of dark nucleon triplets and their dynamics is shadow of dark stringy dynamics very much analogous to text processing?

What if bio-catalysis is induced by dark catalysis based on reconnection as recognition mechanism? What if contractions and expansions of U-shaped flux tubes by heff increasing phase transitions take that reactants find each other and change conformations as in the case of opening of DNA double strand? What if codes allowing only the dark nucleons with same dark nuclear spin and flux tubes spin to be connected by a pair of flux tubes?

This speculation might make sense! The recognition of reactants is one part of catalytic action. It has been found in vitro RNA selection experiments that RNA sequences are produced having high frequency for the codons which code for the amino-acid that these RNA molecules recognize (this). This is just what the proposal predicts!

Genetic codes DNA to RNA as 64→ 64 map, RNA to tRNA as 64→ 40, tRNA to amino-acids with 40→ 20 map are certainly not enough. One can however consider also additional codes allowed by projections of (4⊕ 21⊕ 22) ⊗ (5⊕ 3 (⊕ 1)) to lower-dimensional sub-spaces defined by projections preserving spins. One could also visualize bio-molecules as collections of pieces of text attaching to each other along conjugate texts. The properties of catalysts and reactants would also depend by what texts are "visible" to the catalysts. Could the most important biomolecules participating biochemical reactions (proteins, nucleic acids, carbohydrates, lipids, primary and secondary metabolites, and natural products, see this) have dark counterparts in these sub-spaces.

The selection of bio-active molecules is one of the big mysteries of biology. The model for the chemical pathway leading to the selection of purines as nucleotides (see this) assumes that the predecessor of purine molecule can bind to dark proton without transforming it to ordinary proton. A possible explanation is that the binding energy of the resulting bound state is higher for dark proton than the ordinary one. Minimization of the bound state energy could be a completely general criterion dictating which bio-active molecules can pair with dark protons. The selection of bio-active molecules would not be random after all although it looks so. The proposal for DNA-nuclear/cell membrane as topological quantum computer with quantum computations coded by the braiding of magnetic flux tubes connecting nucleotides to the lipids wlead to the idea that flux tubes being at O=-bonds (see this).

An updated nuclear string variant is summarized and also its connection with the model of harmony is discussed in chapter Three new physics realizations of the genetic code and the role of dark matter in bio-systems and in the article About physical representations of genetic code in terms of dark nuclear strings.

Are sound-like bubbles whizzing around in DNA are essential to life?

I got a link to a very interesting article about sound waves in DNA (see this). The article tells about THz de-localized modes claimed to propagate forth and back along DNA double strand somewhat like bullets. These modes involve collective motion of many atoms. These modes are interpreted as a change in the stiffness of the DNA double strand leading to the splitting of hydrogen bonds in turn leading to a splitting into single strands. The resulting gap is known as transcriptional bubble propagating along double strand is the outcome. I do not how sound the interpretation as sound wave is.

It has been proposed that sound waves along DNA give rise to the bubble. The local physical properties of DNA double strand such as helical structure and elasticity affect the propagation of the waves. Specific local sequences are proposed to favor a resonance with low frequency vibrational modes, promoting the temperary splitting of the DNA double strand. Inside the bubble the bases are exposed to the surrounding solvent, which has two effects.

Bubbles expose the nucleic acid to reactions of the bases with mutagens in the environment whereas so called molecular intercalators may insert themselves between the strands of DNA. On the other hand, bubbles allow proteins known as helicases to attach to DNA to stabilize the bubble, followed by the splitting the strands to start the transcription and replication process. The splitting would occur at certain portions of DNA double strand. For this reason, it is believed that DNA directs its own transcription.

The problem is that the strong interactions with the surrounding water are expected to damp the sound wave very rapidly. Authors study experimentally the situation and report that propagating bubbles indeed exist for frequencies in few THz region. Therefore the damping deo not seem to be effective. How this is possible? As an innocent layman I also wonder how this kind of mechanism can be selective: it would seem that the bullet like sound wave initiates transcription at many positions along DNA. The transcription should be localized to a region assignable to single gene. What could guarantee this?

Can TGD say anything interesting about the mechanism behind transcription and replication?

  1. In TGD magnetic body controls and coordinates the dynamics. The strongest hypothesis is that basic biochemical process are induced by those for dark variants of basic bio-molecules (dark variants of DNA, enzymes,...). The belief that DNA directs its own transcription translates to the statement that the dark DNA consisting most plausibly from sequences of dark proton triplets ppp at dark magnetic flux tubes controls the transcription: the transcription/replication at the level of dark DNA induces that at the level of ordinary DNA.
  2. If the dark DNA codons represented as dark proton triplets (ppp) are connected by 3 flux tube pairs, the reverse of the reconnection should occur and transform flux tube pairs to two U-shaped flux tubes assignable to the two dark DNA strands. Dark proton sequences have positive charge +3e per dark codon giving rise to a repulsive Coulomb force between them. There would be also an attractive force due to magnetic tension of the flux tubes. These two forces would compensate each other in equilibrium (there also the classical forces due to the negatively charged phosphates associated with nucleotides but these would not be so important).

    If the flux tube pairs are split, the stabilizing magnetic force however vanishes and the dark flux tubes repel each other and force the negatively charged DNA strands to follow so that also ordinary DNA strand splits and bubble is formed. The primary wave could therefore be the splitting of the flux tube pairs: whether one can call it as a sound wave is not clear to me. Perhaps the induced propagating splitting of ordinary DNA double strand could be regarded as an analog of sound wave.

    The splitting of flux tube pairs for a segment of DNA would induces a further splitting of flux tubes since repulsive Coulomb force tends to drive the flux tubes further away. The process could be restricted to DNA if the "upper" end of the split DNA region has some dark DNA codons which are not connected by flux tubes pairs. This model reason why for dark proton sequences.

  3. This model does not yet explain how the propagating splitting wave is initiated. Could a quantum phase transition increasing the value of heff associated with the flux tube pairs occur for some minimal portion of dark DNA "below the region associated with gene and lead to the propagating wave induced by the above classical mechanism? That the wave propagates in one direction only could be due to chirality of DNA double helix.
An interesting question is how the RNA world vision relates to this general picture.
  1. There are strong conditions on the predecessor of DNA and RNA satisfies many of them: reverse transcription to DNA making possible transition to DNA dominated era is possible. Double stranded RNA exists in cells and makes possible RNA genome: this would however suggest that cell membrane came first. RNA is a catalyst. RNA has ability to conjugate an amino-acid to the 3' end of RNA and RNA catalyzes peptide bond formation essential for translation. RNA can self-replicate but only relatively short sequences are produced.
  2. TGD picture allows to understand why only short sequences of RNA are obtained in replication. If the replication occurs at the level of dark ppn sequences as it would occur for DNA in TGD framework, long RNA sequences might be difficult to produce because of the stopping of the propagation of the primary wave splitting the flux tube pairs. This could be due to the neuron pairs to which there is associated no Coulomb repulsion essential for splitting.
  3. In TGD framework RNA need not be the predecessor of DNA since the evolution would occur at the level of dark nucleon strings and DNA as the dark proton string is the simpest dark nucleon string and might have emerged first. Dark nuclear strings would have served as templates and biomolecules would have emerged naturally via the transcription of their dark counterparts to corresponding bio-polymers.
An updated nuclear string variant is summarized and also its connection with the model of harmony is discussed in chapter Three new physics realizations of the genetic code and the role of dark matter in bio-systems and in the article About physical representations of genetic code in terms of dark nuclear strings.

Could dark DNA, RNA, tRNA and amino-acids correspond to different charge states of codons?

If dark codons correspond to dark nucleon triplets as assumed in the following considerations there are 4 basic types of dark nucleon triplets: ppp,ppn, pnn, nnn. Also dark nucleons could represent codons as uuu,uud,udd,ddd: the following discussion generalizes as such also to this case. If strong isospin/em charge decouples from spin the spin content is same independently of the nucleon content. One can consider the possibility of charge neuralization by the charges assignable to color flux tubes but this is not necessarily. In any case, one would have 4 types of nucleon triplets depending on the values of total charges.

Could different dark nucleon total charges correspond to DNA,RNA, tRNA and amino-acids? Already the group representation content - perhaps correlating with quark charges - could allow to distinguish between DNA, RNA, tRNA, and amino-acids. For amino-acids one would have only 4× 5 and ordinary statistics and color singlets. For DNA and RNA one would have full multiplet also color non-singlets and for tRNA one could consider (4⊕ 21⊕ 22)× 5 containing 40 states. 31 is the minimum number of tRNAs for the realization of the genetic code. The number of tRNA molecules is known to be between 30-40 in bacterial cells. The number is larger in animal cells but this could be due to different chemical representations of dark tRNA codons.

If the net charge of dark codon distinguishes between DNA,RNA, tRNA, and amino-acid sequences, the natural hypothesis to be tested is that dark ppp, ppn, pnn, and nnn sequences are accompanied by DNA,RNA, tRNA, and amino-acid sequences. The dark beta decays of dark protons proposed to play essential role in the model of cold fusion could transform dark protons to dark neurons. Peptide backbones are neutral so that dark nnn sequence could be also absent but the dark nnn option is more natural if the general vision is accepted.

Is this picture consistent with what is known about charges of amino-acids DNA,RNA, tRNA, and amino-acids?

  1. DNA strand has one negative charge per nucleotide. Also RNA molecule has high negative charge. This conforms with the idea that dark nucleons accompany both DNA and RNA. DNA codons could be accompanied by dark ppp implying charge neutralization in some scale and RNA codons by dark ppn. The density of negative charge for RNA would be 2/3 for that for DNA.
  2. Arg, His, and Lys have positively charged side chains and Asp,Glu negative side chains (see (see this). The charge state of amino-acid is sensitive to the pH value of solution and its conformation is sensitive to the counter ions present. Total charge for amino-acid in peptide however vanishes unless it is associated with the side chain: as in the case of DNA and RNA it is the backbone whose charge is expected to matter.
  3. Amino-acid has central C atom to which side chain, NH2, H and COOH are attached. For free amino-acids in solution water solution NH2→ NH3+ tends to occur pH=2.2 by receiving possibly dark proton whereas COOH tends to become negatively charged above pH= 9.4 by donating proton, which could become dark. In peptide OH attach to C and one H attached to N are replaced with peptide bond. In the pH range 2.2-9.4 amino-acid is zwitterion for which both COOH is negatively charged and NH2 is replaced with NH3+ so that the net charge vanishes. The simplest interpretation is that the ordinary proton from negatively ionized COOH attaches to NH2 - maybe via intermediate dark proton state.
  4. The backbones of peptide chains are neutral. This conforms with the idea that dark amino-acid sequence consists of dark neutron triplets. Also free amino-acids would be accompanied by dark neutron triplets. If the statistics is ordinary only 4 dark nnn states are possible as also 5 dark color flux tube spin states.
  5. tRNA could involve dark pnn triplet associated with the codon. An attractive idea is secondary genetic code assigning RNA codons to tRNA-amino-acid complex and projecting 8⊗ (5⊕ 3) containing 64 dark RNA spin states to 8⊗ 5 containing 40 dark tRNA spin states with same total nucleon and flux tube spins. Dark tRNA codons would in turn be attached to dark amino-acids by a tertiary genetic code projecting spin states 8⊗ 5 to 4⊗ 5 by spin projection. In the transcription dark tRNA would attach to dark mRNA inducing attachment of dark amino-acid to the growing amino-acid sequence and tRNA having only dark tRNA codon would be left. The free amino-acids in the water solution would be mostly charged zwitterions in the pH range 2.2-9.4 and the negative charge of COO- would be help in the attachement of the free amino-acid to the dark proton of tRNA codon. Therefore also the chemistry of free amino-acids would be important.

    An interesting question is why pnn triplets for tRNA would only 5 in flux tube degrees of freedom entire 8 in nucleon degrees of freedom. For RNA consisting of ppn triplets also 3 would be possible. What distinguishes between ppn and pnn?

    An updated nuclear string variant is summarized and also its connection with the model of harmony is discussed in chapter Three new physics realizations of the genetic code and the role of dark matter in bio-systems and in the article About physical representations of genetic code in terms of dark nuclear strings.

About physical representations of genetic code in terms of dark nuclear strings

The standard view about evolution as a random process suggests that genetic code is pure accident. My own view is that something so fundamental as life cannot be based on pure randomness. TGD has led to several proposals for genetic code, its emergence, and various realizations based on purely mathematical considerations or inspired by physical ideas. One can argue that genetic code is realized in several manners just like bits can be represented in very many manners. Two especially interesting proposals have emerged. The first one is based on geometric model of music harmony involving icosahedral and tetrahedral geometries. Second one having two variants is based on dark nuclear strings. Both models predict correctly the numbers of DNA codons coding for a given amino-acid.

An updated nuclear string variant is summarized and also its connection with the model of harmony is discussed in chapter Three new physics realizations of the genetic code and the role of dark matter in bio-systems and in the article About physical representations of genetic code in terms of dark nuclear strings.

Could the replication of mirror DNA teach something about chiral selection?

I received a link to a very interesting popular article from which I learned that short strands of mirror DNA and mirror RNA - known as aptamers - have been be produced commercially for decades - a total surprise to me. Aptamers bind to targets like proteins and block their activity and this ability can be utilized for medical purposes.

Now researchers at Tsinghua University of Beijing have been able to create a mirror variant of an enzyme - DNA polymeraze - catalyzing the transcription of mirror DNA to mirror RNA also replication of mirror DNA. What is needed are the DNA strand to be replicated or transcribed, the mirror DNA nucleotides, and short primer strand since the DNA polymeraze starts to work only if the primer is present. This is like recalling a poem only after hearing the first few words.

The commonly used DNA polymerase containing about 600 amino-adics is too long to be built up as a right-handed version and researchers used a much shorter version: African swine fever virus having only 174 amino-acids. The replication turned out to be very slow. A primer of 12 nucleotides was extended to a strand of 18 nucleotides in about 4 hours: 3/2 nucleotides per hour. The extension to a strand of 56 nucleotides took 36 hours making 44/36= 11/9 nucleotides per hour. DNA and its mirror image co-existed peacefully in a solution. One explanation for the absence of mirror life is that the replication and transcription of mirror form was so slow that it lost the fight for survival. Second explanation is that the emergence of mirror forms of DNA polymerase and other enzymes was less probable.

Can one learn anything about this?

  1. Chiral selection is one of the deep mysteries of biology. Amino-acids are left-handed and DNA and RNA double strands form a right-handed screw. One can assign handedness with individual DNA nucleotides and with DNA double strand but web sources speak only about the chirality of double strand. If the chirality of the DNA nucleotides were not fixed, it would have been very probably discovered long time ago as an additional bit doubling the number of DNA letters.
  2. What could be the origin of the chirality selection? Second helicity could have been loser in the fight for survival and the above finding supports this: fast ones eat the slow ones like in market economy. There must be however a breaking of mirror symmetry. Weak interactions break of mirror symmetry but the breaking is extremely small because the weak bosons mediating weak interaction are so massive that the length scale in which the breaking of mirror symmetry matters is of order 1/100 times proton size. This breaking is quite too small to explain chiral selection occurring in nano-scales: there is discrepancy of 8 orders of magnitude. The proposal has been that the breaking of mirror symmetry has been spontaneous and induced by a very small seed. As far as I know, no convincing candidate for the seed has been identified.
According to TGD inspired model chiral selection would be induced from that in dark matter sector identified in terms of phases of ordinary matter with non-standard value of Planck constant heff/h= n. In living matter dark matter would reside at magnetic flux tubes and control ordinary matter. TGD predicts standard model couplings, in particular weak parity breaking. For heff/h= n the scale below which weak bosons behave as massless particles implying large parity breaking is scaled up by n. Large parity breaking for dark matter becomes possible in even biological length scales for large enough heff.

The crucial finding is that the states of dark proton regarded as part of dark nuclear string can be mapped naturally to DNA, RNA, tRNA, and amino-acid molecules and that vertebrate genetic code can be reproduced naturally. This suggests that genetic code is realized at the level of dark nuclear physics and induces its chemical variant. More generally, biochemistry would be kind of shadow of dark matter physics. A model for dark proton sequences and their helical pairing is proposed and estimates for the parity conserving and breaking parts of Z0 interaction potential are deduced.

For details see the article Could the replication of mirror DNA teach something about chiral selection? or the chapter Evolution in many-sheeted space-time of "Genes and Memes".

One step further in the understanding the origins of life

I learned about very interesting discovery related to the problem of understanding how the basic building bricks of life might have emerged. RNA (DNA) has nucleotides A,G,C,U (T) as basic building bricks.

The first deep question is how the nucleotides A,G,C,U, and T emerged.

  1. There are two types of nucleotides. Pyrimidines C and T/U ) have single carbon 6-cycle. Purines A and G in turn have single 6-single and 5-cycle fused attached together along one side. Purines are clearly more complex than pyrimidines.
  2. U.K. chemist John Sutherland demonstrated a plausible sequence of steps leading to the emergence of pyrimidines. Purines turned out to be more problematic. Leslie Orgel and colleagues suggested a possible pathway but it produces purines in too tiny amounts.
Now a group led by Thomas Carell in Ludwig Maximilian University have found a more plausible mechanism.
  1. Carell and colleagues studied the interaction of biomolecule formamido-pyrimidine (FaPy) with DNA and found that it also reacts to produce purines. Could FaPys have served as predecessors of purines? (For formamide see this and for the class of chemical compounds known as amines see this).
  2. The first step would have been a copious production of amino-pyrimidines containing several chemical groups known as amines. The problem is that the are so many amines and they normally react indiscriminantly to produce many different compounds. One wants mostly purines so that only one critical amine is wanted.
  3. When Carell and his team added some acid to the solution to decrease its pH, a miracle happened. The extra protons from acid attached to the amines of the amino-pyrimidine and made them non-reactive. There was however one exception: just the amine giving rise to purine in its reactions! The reactive amine also readily bonded with formic acid or formamide. Hence it seems that one big problem has been solved.
The second challenge is to understand how the building bricks of RNA and DNA combined to form longer polymers and began to replicate.
  1. One prevailing vision is that so called RNA world preceded the recent biology dominated by DNA. The goal has been to achieve generation of RNA sequence in laboratory. Unlike DNA RNA sequences are not stable and long sequences are difficult to generate. DNA in turn replicates only inside cell and the presence of what is known as ordered water seems to be essential for this.
  2. This step might involve new physics and chemistry and I have considered the possibility that the new physics involves magnetic bodies and dark proton sequences as a representation of the genetic code at the level of dark nuclear physics. There is no need to add that the fact that dark proton states provide representations for RNA, DNA, tRNA, and amino-acids (see this) looks like a miracle and I find still difficult to believe that it is true and for genetic code. Also the representation of vertebrate code emerges in terms of correspondences of dark proton states.

    This suggests that the replication of DNA and takes place at the level of dark proton sequencies - dark nuclear strings - serving as a dynamical template for the biological replication. Also transcription and translation would be induced by dark process. Actually all biochemical processes could have as template the dynamics of molecular magnetic bodies and biochemistry would be kind of shadow of deeper dynamics.

  3. There is actually support for dark proton sequences. Quite recently I learned about the article of Leif Holmlid and Bernhard Kotzias (see this) about the superdense phase of hydrogen. In TGD superdense phase has interpretation as dark proton sequences at magnetic flux tubes with the Compton length of dark proton coded by heff/h≈ 211 to electron's Compton length (see this). Remarkably, it is reported that the superdense hydrogen is super-conductor and super-fluid at room temperatures and even above: this is just what TGD predicts.

    The dark protons in TGD inspired quantum biology (see this) should have much longer Compton length of order of the distance between nucleotides in DNA sequences in order to serve as templates for chemical DNA. This gives a dark Compton length of order ≈ 3.3 Angstroms from the fact that there are 10 codons per 10 nm. This gives heff/h≈ 218 .

One can return back to the first step in the genesis of DNA and RNA. The addition of protons to the solution used to model prebiotic environment to make it slightly acidic was the key step. Why?
  1. Here cold fusion might help. Cold fusion is claimed to take place in electrolysis involving ionization and charge separation. The electric fields used in electrolysis induce ionization and thus charge separation. For me it has however remained a mystery how electric fields, which are extremely tiny using the typical strength of molecular electric field as standard are able to induce a charge separation. Of course, every chemist worth of his salt regards this as totally trivial problem. I am however foolish enough to consider the possibility that some new physics might be involved.
  2. The mechanism causing charge separation could be analogous to or that discovered by Pollack as he irradiated water bounded by a gel phase (see this): in the recent case the electric field would take the role of irradiation as a feeder of energy. Negatively charged exclusion zones (EZs) were formed and 1/4 of protons went somewhere.

    The TGD proposal (see this) is that part of protons went to magnetic flux tubes and formed dark proton sequences identifiable as dark nuclear strings. The scaled down nuclear binding energy favours the formation of dark nuclear strings perhaps proceeding as analog of nuclear chain reaction. This picture allows to ask whether dark proton sequences giving rise to a fundamental representation of the genetic code could have been present already in water (see this).

  3. How DNA/RNA could have then formed? Could the protons making the solution acidic be dark so that the proton attaching to the amine would be dark? Could it be that for all amines except the right one the proton transforms to ordinary proton and destroys the chemical reactivity. Could the attached dark proton remain dark just for the correct amine so that the amine would remain reactive and give rise to purine in further reactions? Could A,G,C,T and U be those purines and pyrimidines - or even more general biomolecules - for which the attachment to dark proton does not transform it to ordinary proton and in this manner affect dramatically the chemical properties of the molecule? What is the condition for the preservation of the darkness of the proton?

See the chapter Prebiotic evolution in many-sheeted space-time or the article One step further in the understanding the origins of life.

RNA is transferred between soma cells and germ cells

There was a highly interesting popular article No Sex Required: Body Cells Transfer Genetic Info Directly Into Sperm Cells, Amazing Study Finds summarizing the findings discussed in the article Soma-to-Germline Transmission of RNA in Mice Xenografted with Human Tumour Cells: Possible Transport by Exosomes.

The abstract of the article gives for a professional a readable summary. Mendelian laws provide the universal founding paradigm for the mechanism of genetic inheritance through which characters are segregated and assorted. In recent years, however, parallel with the rapid growth of epigenetic studies, cases of inheritance deviating from Mendelian patterns have emerged. Growing studies underscore phenotypic variations and increased risk of pathologies that are transgenerationally inherited in a non-Mendelian fashion in the absence of any classically identifiable mutation or predisposing genetic lesion in the genome of individuals who develop the disease. Non-Mendelian inheritance is most often transmitted through the germline in consequence of primary events occurring in somatic cells, implying soma-to-germline transmission of information. While studies of sperm cells suggest that epigenetic variations can potentially underlie phenotypic alterations across generations, no instance of transmission of DNA- or RNA-mediated information from somatic to germ cells has been reported as yet.

To address these issues, we have now generated a mouse model xenografted with human melanoma cells stably expressing EGFP-encoding plasmid. We find that EGFP RNA is released from the xenografted human cells into the bloodstream and eventually in spermatozoa of the mice. Tumor-released EGFP RNA is associated with an extracellular fraction processed for exosome purification and expressing exosomal markers, in all steps of the process, from the xenografted cancer cells to the spermatozoa of the recipient animals, strongly suggesting that exosomes are the carriers of a flow of information from somatic cells to gametes. Together, these results indicate that somatic RNA is transferred to sperm cells, which can therefore act as the final recipients of somatic cell-derived information.

Some background is needed to understand this rather technical summary.

  1. Darwinism has dominated biology since Darwin. The rules of classical Mendelian inheritance conform with the Darwinian view and can be reduced to genetic level. Various traits are inherited genetically by sexual reproduction and genome would change during lifetime only through mutations. Genome changes exremely slowly by random changes for offspring from which selection pressures choose the survivors.

    Lamarckian view in turn assumed that the external circumstances experienced by organism leave a trace, which can be inherited but it could not be formulated in terms of modern molecular biology whereas the Darwinian dogma could be formulated in terms of Weissman's genetic barrier. Information flows from germ cells to soma but never in opposite direction. If it would do so, the soma interacting with environment could transfer information to germ cells and the experiences during lifetime could leave inheritable trace to germ cells.

    An analogous dogma is that information is always transcribed from DNA to RNA to proteins but never in opposite direction. It is now known that this takes place in case of viruses and retroviruses: there are so called jumping genes which can also make copies of themselves. 5 per cent of human genome conists of endogenous retroviruses capable of doing the same. The huge genome of maize is due to this kind of proces.

  2. The development epigenetics has started to shatter the belief on Wessimann's genetic barrier. Gene expression is not fixed by genome alone and can be change even when genes are unaffected. Silencing of genes by DNA methylation and histone modification allow to modify gene expression. Silencing is essentially a locking of gene preventing its expression by transcription followed by translation.

    It is now known that epigenetic changes in the gene expression can be inherited. The mechanisms are still poorly understood. What seems however clear the genome is more like a slowly changing hardware and gene expression or whatever is behind it is the software and programs can change very rapidly by just adding or deleting comment signs in the code. A deeper understanding of this software is needed.

  3. Epigenetic inheritance requires that genetic information is transferred from soma cells to germ cells. If only DNA or RNA are capable of representing genetic information, then DNA or RNA must be transferred from soma cells to germ cells. No instance of direct DNA or RNA mediated information from soma to germ cells had been observed before the above mentioned experiments. One can of course challenge the assumption about DNA and RNA as the only representations of genetic information.
The basic idea of the experiment was simple. Use a marker for RNA by using plasmids (DNA strands not belonging to chromosomes) genetically engineered to code for a marker protein making itself visible by fluoresence. Then one just follows the fate of these proteins generated in soma cells and looks whether they end up inside germ cells and how this happens.

More technically: mouse model was xenografted with human melanoma cells stably expessing EGFP-coding plasmid (expressed in a manner possibly evoking emotions: human melanoma cancer tissue was implanted in mouse). EGFP-RNA is released from xenografted human cells to blood. One just looks whether it eventually ends up to the sperm cells of mice and tries to identify the transfer mechanism. Only transfer to sperm cells was studied. One might expect that the transfer of RNA can happen also to ovum. I guess that the sperm cells are easier to study.

What was observed?

  1. The transfer of RNA from soma cells to sperm cells was indeed found to occur. The transferred RNA can in turn induce epigenetic effects in germ cells known to be inherited by a mechanisms, which however remain poorly understood. Epigenetic mechanisms seem to be involved in the cases considered so that DNA is not changed, only its expression.
  2. The transfer mechanism was identified. The transferred RNA is contained by exosomes analogous to synaptic vesicles transferring neurotransmitters from presynaptic to postsynaptic cell. Transfer of RNA takes place via fusion of the membranes just like transfer of neurotransmitters. Maybe genetic engineering using exosomes or analogous structures to transfer the needed material to cells has been tried.
The implications of the findings are dramatic but already implied by the earlier work in epigenetics. What is important that Lamarckian view can be now defended by a concrete genetic mechanism. Lamarckism implies that the time scale of inheritance becomes the time scale for the appearence of a new generation. Nutrition, environment, lifestyle and even meditation and similar practices, are already now known to affect gene expression on daily basis: we are not victims of genetic determinism and are epigenetically responsible for our own well-being. Epigenetic information can be transferred also to germ cells so that we responsible also for the well-being of our children. Our children suffer our sins and share our sufferings.

The precise mechanism of inheritance of epigenetic modifications is poorly understood. For instance, it is known that alleles (variants of game gene) can express themselves differently: this would be due to epigenetics. One allele can also induce other allele to express in the same manner. Somekind of "social pressure" like interaction seems to be involved.

TGD suggests the notion of magnetic body and cyclotron resonance as this interaction. The DNA of offspring get tuned to the DNA of mother during pregnancy and this gives to epigenetic inheritance. Various epigenetic mechanisms such as methylation and histone modification could affect cyclotron frequencies besides purely geometric modifications of DNA and locking at the level of gene could be accompanied kicking out of tune at the level of magnetic body. These aspects are discussed in earlier blog posting and the article Magnetic body, bio-harmonies, morphogenesis, and epigenetics.

See the article Magnetic body, bio-harmonies, morphogenesis, epigenetic or the chapter Three new physics realizations of the genetic code and the role of dark matter in bio-systems.

E8 symmetry, harmony, and genetic code

Bee gave in Facebook a link to an article about a connection between icosahedron and E8 root system (see this). The article (I have seen an article about the same idea earlier but forgotten it!) is very interesting.

The article talks about a connection between icosahedron and E8 root system. Icosahedral group has 120 elements and its double covering 2× 120=240 elements. Remarkably, E8 root system has 240 roots. E8 Lie algebra is 248 complex-dimensional contains also the 8 commuting generators of Cartan algebra besides roots: it is essential that the fundamental representation of E8 co-incides with its adjoint representation. The double covering group of icosahedral group acts as the Weyl group E8. A further crucial point is that the Clifford algebra in dimension D=3 is 8-D.

One starts from the symmetries of 3-D icosahedron and ends up with 4-D root system F4 assignable to Lie group and also to E8 root system. E8 defines a lattice in 8-D Euclidian space: what is intriguing that dimensions 3,4, 8 fundamental in TGD emerge. To me this looks fascinating - the reasons will be explained below.

What I might have understood

I try to explain what I have possibly understood.

  1. The notion of root system is introduced. The negatives of roots are also roots but not other multiples. Root system is crystallographic if it allows a subset of roots (so called simple roots) such that all roots are expressible as combinations of these simple roots with coefficients having the same sign. Crystallographic root systems are special: they correspond to the fundamental weights of some Lie algebra. In this case the roots can be identified essentially as the quantum numbers of fundamental representations from which all other representations are obtained as tensor products. Root systems allow reflections as symmetries taking root system to itself. This symmetry group is known as Coxeter group and generalizes Weyl group. Both H3 and H4 are Coxeter groups but not Weyl groups.
  2. 3-D root systems known as Platonic roots systems (A3, B3, H3) assignable to the symmetries of tetrahedron, octahedron (or cube), and icosahedron (or dodecahedron) are constructed. The root systems consist of 3 suitably chosen unit vectors with square equal to 1 (square of reflection equals to one) and the Clifford algebra elements generated by them by standard Clifford algebra product. The resulting set has a structure of discrete group and is generated by reflections in hyper-planes defined by the roots just as Weyl group does. This group acts also on spinors and one obtains a double covering SU(2) of rotation group SO(3) and its discrete subgroups doubling the number of elements. Platonic symmetries correspond to the Coxeter groups for a "Platonic root system" generated by 3 unit vectors defining the basis of 3-D Clifford algebra. H3 is not associated with any Lie algebra but A3 and B3 are.

    Pinors (spinors) correspond to products of arbitrary/even number of Clifford algebra elements. They mean something else than usually a bein identified as elements of the Clifford algebra acting and being acted on from left or right by multiplication so that they always behave like spin 1/2 objects since only the left(right)-most spin is counted. The automorphisms involve both right and left multiplication reducing to SO(3) action and see the entire spin of the Clifford algebra element.

  3. The 3-D root systems (A3, B3, H3) are shown to allow an extension to 4-D root systems known as (D4, F4, H4) in terms of 3-D spinors. D4 and F4 are root systems of Lie algebras (see this). F4 corresponds to non-simply-laced Lie group related to octonions. H4 is not a root system of any Lie algebra.

  4. The observation that the dimension of Clifford algebra of 3-D space is 23=8 and thus allows imbedding of at most 8-D root system must have inspired the idea that it might be possible to construct the root system of E8 in 8-D Clifford algebra from 240 pinors of the double covering the 120 icosahedral reflections. Platonic solids would be behind all exceptional symmetry groups since E6 and E7 are subgroups of E8 and the construction should give their root systems also as low-dimensional root systems.

Mc Kay correspondence

The article explains also McKay correspondence stating that the finite subgroups of rotation group SU(2) correspond to simply laced affine algebras assignable with ADE Lie groups.

  1. One considers the irreducible representations of a finite subgroup of the rotation group. Let the number of non-trivial representations be m so that by counting also the trivial representation one has m+1 irreps altogether. In the Dynkin diagram of affine algebra of group with m-D Cartan algebra the trivial representation corresponds to the added node. One decomposes the tensor product of given irrep with the spin 2 representation into direct sum of irreps and constructs a diagram in which the node associated with the irrep is connected to those nodes for which corresponding representation appears in the direct sum. One can say that going between the connected nodes corresponds to forming a tensor product with the fundamental representation. It would be interesting to know what happens if one constructs analogous diagrams by considering finite subgroups of arbitrary Lie group and forming tensor products with the fundamental representation.
  2. The surprising outcome is that the resulting diagram corresponds to a Dynkin diagram of affine (Kac-Moody) algebra of ADE group with Cartan algebra, whose dimension is m. Cartan algebra elements correspond to tensor powers of fundamental representation: can one build any physical picture from this? For m= 6,7,8 one obtains E6, E7, E8. The result of the article implies that these 3 Lie-groups correspond to basis of 3 3-D unit identified as units of Clifford algebra: could this identification have some concrete meaning as preferred non-orthogonal 3-basis?
  3. McKay correspondence emerges also for inclusions of hyper-finite factors of type II1. The integer m characterizing the index of inclusion corresponds to the dimensions of Cartan algebra for ADE type Lie group. The inclusions of hyperfinite factors (HFFs) are characterized by integer m≥3 giving the dimension of Cartan algebra of ADE Lie groups (there are also C, F and G type Lie groups). m= 6,7,8 corresponds to exceptional groups E6, E7, E8 on one hand and to the discrete symmetry groups of tetrahedron, octahedron, icosahedron on the other hand acting as symmetries of corresponding 3-D non-crystallographic systems and not allowing interpretation as Weyl group of Lie group.

Connection with the model of harmony

These findings become really exciting from TGD point of view when one recalls that the model for bioharmony ( for 12-note harmonies central in classical music in general relies on icosahedral geometry. Bioharmonies would add something to the information content of the genetic code: DNA codons consisting of 3 letters A,T,C,G would correspond to 3-chords defining given harmony realized as dark photon 3-chords and maybe also in terms of ordinary audible 3-chords. This kind of harmonies would be roughly triplets of 3 basic harmonies and there would be 256 of them (the number depends on counting criteria). The harmonies could serve as correlates for moods and emotional states in very general sense: even biomolecules could have "moods". This new information should be seen in biology. For instance, different alleles of same gene are known to have different phenotypes: could they correspond to different harmonies? In epigenetics the harmonies could serve as a central notion and allow to realize the conjectured epigenetic code and histone code. Magnetic body and dark matter at them would be of course the essential additional element.

The inspiring observations are that icosahedron has 12 vertices - the number of notes in 12-note harmony and 20 faces- the number of amino-acids and that DNA codons consist of three letters - the notes of 3-chord.

  1. Given harmony would be defined by a particular representation of Pythagorean 12-note scale represented as self-non-intersecting path (Hamiltonian cycle) connecting the neighboring vertices of icosahedron and going through all 12 vertices. One assumes that neighboring vertices differ by one quint (frequency scaling by factor 3/2): quint scale indeed gives full octave when one projects to the basic octave. One obtains several realizations (in the sense of not being related by isometry of icosahedron) of 12-note scale. These realizations are characterized by symmetry groups mapping the chords of harmony to chords of the same harmony. These symmetry groups are subgroups of the icosahedral group: Z6, Z4, and two variants of Z2 (generated by rotation of π and by reflection) appear. Each Hamiltonian cycle defines a particular notion of harmony with allowed 3-chords identified by the 20 triangles of icosahedron.

  2. Pythagoras is trying to whisper me an unpleasant message: the quint cycle does not quite close! This is true. Musicologists have been suffering for two millenia of this problem. One must introduce 13th note differing only slightly from some note in the quint cycle. At geometrical level one must introduce tetrahedron besides icosahedron - only four notes and four chords and gluing along one side to icosahedron gives only one note more. One can keep tetrahedron also as disjoint from icosahedron as it turns out: this would give 4-note harmony with 4 chords something much simpler that 12- note harmony.

  3. The really astonishing discovery was that one can understand genetic code in this framework. First one takes three different types of 20-chord harmonies with group Z6, Z4, and Z2 defined by Hamiltonian cycles: this can be done in many different maners (there are 256 of them). One has 20+20+20 chords and one finds that they correspond nicely to 20+20+20=60 DNA codons: DNA codons coding for a given amino-acid correspond to the orbit of the triangle assigned with the amino-acid under the symmetry group of harmony in question.

    The problem is that there are 64 codons, not 60. The introduction of tetrahedron brings however 4 additional codons and gives 64 codons altogether. One can map the resulting 64 chord harmony to icosahedron with 20 triangles (aminoacids) and the degeneracies (number of DNA codons coding for given amino-acid in vertebrate code) come out correctly! Even the two additional troublesome amino-acids Pyl and Sec appearing in Nature and the presence of two variants of genetic code (relating to two kinds of Z2 subgroups) can be understood.

What could the interpretation of the icosahedral symmetry?

An open problem is the proper interpretation of the icosahedral symmetry.

  1. A reasonable looking guess would be that it quite concretely corresponds to a symmetry of some biomolecule: both icosahedral or dodecahedral geometry give rise to icosahedral symmetry. There are a lot of biomolecules with icosahedral symmetry, such as clathrate molecules at the axonal ends and viruses. Note that dodecahedral scale has 20 notes - this might make sense for Eastern harmonies - and 12 chords and there is only single dodecahedral Hamiltonian path found already by Hamilton and thus only single harmony. Duality between East and West might exist if there is mapping of icosahedral notes and to dodecahedral 5-chords and dodecahedral notes to icosahedral 3-chords and different notions of harmony are mapped to different notions of melody - whatever the latter might mean!).
  2. A more abstract approach tries to combine the above described pieces of wisdom together. The dynamical gauge group E8 (or Kac-Moody group) emerging for m=8 inclusion of HFFs is closely related to the inclusions for the fractal hierarchy of isomorphic sub-algebras of super-symplectic subalgebra. heff/h=n could label the sub-algebras: the conformal weights of sub-algebra are be n-multiples of those of the entire algebra.

    The integers ni resp. nf for included resp. including super conformal sub-algebra would be naturally related by nf= m× ni. m=8 would correspond to icosahedral inclusion and E8 would be the dynamical gauge group characterizing dark gauge degrees of freedom. The inclusion hierarchy would allow to realize all ADE groups as dynamical gauge groups or more plausibly, as Kac-Moody type symmetry groups associated with dark matter and characterizing the degrees of freedom allowed by finite measurement resolution.

  3. E8 as dynamical gauge group or Kac-Moody group would result from the super-symplectic group by dividing it with its subgroup representing degrees of freedom below measurement resolution. E8 could be the symmetry group of dark living matter. Bioharmonies as products of three fundamental harmonies could relate directly to the hierarchies of Planck constants and various generalized super-conformal symmetries of TGD! This convergence of totally different theory threads would be really nice!
Experimental indications for dynamical E8 symmetry

Lubos (thanks to Ulla for the link to the posting of Lubos) has written posting about experimental finding of E8 symmetry emerging near the quantum critical point of Ising chain at quantum criticality at zero temperature. Here is the abstract :

Quantum phase transitions take place between distinct phases of matter at zero temperature. Near the transition point, exotic quantum symmetries can emerge that govern the excitation spectrum of the system. A symmetry described by the E8 Lie group with a spectrum of eight particles was long predicted to appear near the critical point of an Ising chain. We realize this system experimentally by using strong transverse magnetic fields to tune the quasi–one-dimensional Ising ferromagnet CoNb2O6 (cobalt niobate) through its critical point. Spin excitations are observed to change character from pairs of kinks in the ordered phase to spin-flips in the paramagnetic phase. Just below the critical field, the spin dynamics shows a fine structure with two sharp modes at low energies, in a ratio that approaches the golden mean predicted for the first two meson particles of the E8 spectrum. Our results demonstrate the power of symmetry to describe complex quantum behaviors.

Phase transition leads from ferromagnetic to paramagnetic phase and spin excitations as pairs of kinks are replaced with spin flips (shortest possible pair of kinks and loss of the ferromagnetic order). In attempts to interpret the situation in TGD context, one must however remember that dynamical E8 is also predicted by standard physics so that one must be cautious in order to not draw too optimistic conclusions.

In TGD framework heff/h> 1 phases or phase transitions between them are associated with quantum criticality and it is encouraging that the system discussed is quantum critical and 1-dimensional.

  1. The large value of heff would be associated with dark magnetic body assignable to the magnetic fields accompanying the E8 "mesons". Zero temperature is not a prerequisite of quantum criticality in TGD framework.
  2. One should clarify what quantum criticality exactly means in TGD framework. In positive energy ontology the notion of state becomes fuzzy at criticality. For instance, it is difficult to assign the above described "mesons" with either ferromagnetic or paramagnetic phase since they are most naturally associated with the phase change. Hence Zero Energy Ontology (ZEO) might show its power in the description of (quantum) critical phase transitions.

    Quantum criticality could correspond to zero energy states for which the value of heff differs at the opposite boundaries of causal diamond (CD). Space-time surface between boundaries of CD would describe the transition classically. If so, then E8 "mesons" would be genuinely 4-D objects - "transitons" - allowing proper description only in ZEO. This could apply quite generally to the excitations associated with quantum criticality. Living matter is key example of quantum criticality and here "transitons" could be seen as building bricks of behavioral patterns. Maybe it makes sense to speak even about Bose-Einstein condensates of "transitons".

    The finding suggests that quantum criticality is associated with the transition increasing neff by factor m=8 or its reversal - maybe the standard value neff(i) =1. neff(f) =8 could correspond to the ferromagnetic phase having long range correlations. Could one could say that at the side of criticality (say the "lower" end of CD) the neff(f)=8 excitations are pure gauge excitations and thus "below measurement resolution" but become real at the other side of criticality (the "upper" end of CD)?

  3. The 8 "mesons" associated with spin excitations naturally correspond to the generators of the Cartan algebra of E8. If the "mesons" belong to the fundamental (= adjoint) representation of E8, one would expect 120+120 additional particles with non-vanishing E8 charges. Why only Cartan algebra? Is the reasons that Cartan algebra is in preferred role in the representations of Kac-Moody algebras in that charged Kac-Moody generators can be constructed from Cartan algebra generators by standard construction used also in string models. Could this explain why one expects only 8 "mesons". Are charged "mesons" labelled by the elements of double covering of icosahedral group more difficult to excite?
See the article E8 symmetry, harmony, and genetic code or the chapter Three new physics realizations of the genetic code and the role of dark matter in bio-systems.

Magnetic body, bio-harmonies and epigenetics

What TGD can possibly give to biology is the vision about magnetic body as an intentional agent using biological body as a sensory receptor and motor instrument and about various mechanism used by magnetic body for control and communication purposes. A new element is brought in by Zero Energy Ontology: magnetic body is 4-dimensional and thus correlate for a behavioral pattern rather than 3-D state for part of organism. Also the notion of bio-harmony suggests itself as a correlate for quantum coherence at the level of basic bio-molecules. The discussion below raises and tries to answer general questions.

The finding that behavioral patterns of planaria can be remembered also by the piece of split planaria without brains is consistent with the idea that replication of magnetic body coding for behaviors is behind biochemical replication. That alleles of the same gene have different expression could be understood if the bio-harmony assignable to gene carries additional information besides the biochemical information.

These notions might also provide a fresh approach to epigenetics. Histone modification and DNA methylation are believed to induce kind of geometric locking preventing transcription. They could also affect the frequency assignable to DNA codon or some key unit so that the resonance condition making possible reconnection of U-shaped flux tubes allowing biomolecules to get in contact fails and transcription cannot proceed. Epigenetic inheritance could reduce to the inheritance of bio-harmony: the magnetic bodies of cells of offspring get in tune with those of parent. To how high degree magnetic body and bio-harmony are inherited? This becomes the key question.

1. Basic ideas related to magnetic body

Consider first some key ideas of TGD inspired quantum biology.

  1. In TGD framework magnetic body extends the pair formed by organism and environment to a kind of holy trinity. Magnetic flux tubes and the realization of genetic code in terms of dark proton sequences has been the key hypothesis. The model for cold fusion suggests that also more general dark nuclei must be allowed. Dark neutron sequences could correspond to genes separated by dark protons. Dark weak interactions with large value of heff effectively massless below neuron size scale would play central role and induce large parity breaking effects (chiral selection).

    The chemistry of DNA and tRNA would not be all that matters. DNA-nuclear/cell membrane as topological quantum computer with braided magnetic flux tubes would explain why organisms with virtually identical genomes are so different (we and our ancestors for instance). The hierarchy of magnetic bodies would be responsible for the development of intelligence and for cultural evolution. Flux tubes connecting DNA and mRNA as well as mRNA and tRNA molecules are present but it is difficult to say anything concrete.

  2. During the process of making sense of the abstract of the article, I learned that ontogeny can be seen as a kind of editing process for the text defined by the DNA. Control of control of... is involved so that situation is very complex. Who performs the editing? Does DNA edit itself and is the editing process defining evolution of genome coded by genome? Or is the editing performed by Darwinian selection at cell level? Or is the magnetic body the editor using genome also as its tool as TGD would suggest? What is important that in TGD framework self-organization in 4-D sense implied by Zero Energy Ontology replaces ordinary self-organization leading to asymptotic spatial patterns and select spatiotemporal patterns as asymptotic behavioral patterns defining various biological functions. The role of magnetic body is central in this process.
  3. Magnetic body contains cyclotron Bose-Einstein condensates and cyclotron frequencies determined by the strength of magnetic field would give for DNA and other biomolecules additional characteristics. In TGD based model for musical harmony DNA codons would correspond quite concretely to 3-chords but played using dark photons (also ordinary music represented as sounds could be transformed to dark photon music). If one accepts the icosahedral model of bio-harmonies predicting genetic code correctly, there would be 256 fundamental harmonies characterised by the allowed collection of 3-chords and they would add to the information carried by DNA molecules. I have constructed a program building random sequences of the allowed chords using the additional harmonic rule that two subsequent chords contain at least one common note and this music sounds rather harmonic (albeit boring in absence of any other elements!)
  4. Could one distinguish between different states/phases of DNAs, mRNAs, tRNAs, and amino acids in terms of harmony? Could their functioning depend on the harmony? With the inspiration coming from the connection of emotions and musical harmonies I have proposed that the harmony associated with a gene or organ could correlate with something analogous to an emotional state or mood - maybe micro-mood or microemotion could be the proper notion. Could amino-acids be happy, hilarious, melancholic, sad, depressed? Could one distinguish between different phases of DNA, RNA, tRNA, aminoacid collections characterized by the harmony in turn characterizing the of a cell, organelle, organ, or even organism? tRNA defines the map of the harmony associated with DNA codons to amino-acid harmony. Is the information about DNA codon and about corresponding 3-chord represented at the level of magnetic body of amino-acid- that is as the 3-chord, which it represents, and realized as the rules telling with which tRNAs amino-acid can reconnect?

    In contrast to DNA codons, which represent local information, harmony could represent holistic information and characterize entire genes or their intronic portions.

2. Problem

There is however a problem. DNA codons coding for the same amino-acid correspond to different 3-chords of harmony. One of these chords corresponds to amino-acid itself and the codons coding for amino-acid correspond to the orbit of this chord under subgroup of isometries of icosahedron moving the triangles of icosahedron along the orbit. This would apply also to mRNA and maybe also to tRNA. The chords at the orbit of amino-aicid are isomorphic (intervals are same) and obtained as transposes of each other.

The chords are isomorphic but not identical and this leads to the problem with resonance paradigm unless one gives up the idea that amino-acid corresponds to a unique DNA codon and assumes that there is analog of gauge invariance allowing to choose the preferred codon freely.

  1. The assumption about preferred DNA codon could be given up if one can choose the preferred DNA codon freely so that also the magnetic bodies of amino-acids are characterized by 3-chords and thus carry information about what DNA codon coded them. This is possible if one has the analog of fiber space structure with DNA codons coding for amino-acid defining the fiber and amino-acids defining the base. This fiber structure with discrete gauge invariance is strongly suggestive and I have proposed it for two decades ago but it seems that it poses strong conditions on the orbits of the subgroups of isometries of icosahedron.

    This condition is very restrictive. Simplifying somewhat: one considers 60 codons decomposing into 20+20+20 codings and each group of 20 codons codes for amino-acids belonging to different groups. There are twenty of them. The 20 triangles of icosahedron correspond to 3 DNA codons each and each of them corresponds to one and only one amino-acid. One has 3 subgroups of isometries corresponding to 20+20+20 decomposition.

    Can one perform a global gauge transformations realized as isometries and moving triangles along the orbits of one of the 3 subgroups involved - say isometry g1 of G1? These transformations would move the entire orbits of 2 subgroups involved - call them G2 and G3. What happens to the chords of G2 and G3: is their character changed completely so that these harmonies would be destroyed? It seems that this cannot work. Should one replace G2 and G3 with their automorphs g1G2g1-1 and g1G3g1-1. Does this make sense? 3-chords defining give orbit should be invariant under automorphisms of Gi? This does not seem to be a realistic condition.

  2. Could different automorphs correspond to different collections of chords physically just as global gauge transformations generate different physical situations? Isometries of groups Gi would therefore define physically different realizations of bio-harmonies such that for each of them only one of the DNA codons coding for given amino-acid could actually perform the coding. Ordinary genetic code with many-to-one correspondence would make sense in statistical sense only. If this is true, the cyclotron frequency 3-chord assignable to amino-acid depends on the DNA coding it and implies physical distinctions.
  3. One can consider also a third alternative. DNA codon with same 3-chord as coding for amino-acid is in special role in that only it can resonate with the amino-acid! Could DNA codons codons correspond to same cyclotron frequency triplet (magnetic fields) but different value of heff so that one would have chord with respect to energy rather than frequency. Different values of heff for DNA codons coding for the same amino-acid would scale their cyclotron frequencies to the same amino-acid frequency while keeping cyclotron energies invariant? Cyclotron energy ratios for codons correspond to rational valued ratios Ei/Ej = heff(i)/heff(j)= n(i)/n(j). Amino-acid would correspond to fixed heff and this creates a problem: can DNA codon code for amino-acid with different value of heff. This option does not look attractive.
Second option looks most plausible. Of course, it is early to talk about a prediction: it might well be that I have mis-understood something.

3. Questions about bio-harmony

One can pose a lot of questions about bio-harmony.

  1. It is not necessary to assign any interpretation on the harmony. Just the harmony could be enough if it is forced to be same for DNA, corresponding mRNA, tRNA, and aminoacids. One can however make questions. Is the harmony inherited invariant and could it distinguish between different personality types about which we learned in old books of psychology? Or could the harmonies correlate with our own moods?
  2. Could differentiation selecting particular genes as expressed genes apply also to harmonies so that given gene would correspond only to a particular harmony and different copies of gene could correspond to different harmonies. Could this selection rely on the same mechanisms as ordinary differentiation realized in terms of epigenetic mechanisms and DNA editing? From the magnetic bodies of genes the harmony would be automatically transferred to the magnetic bodies of mRNA, tRNA and aminoacids since otherwise the transcription and translation do not work since magnetic bodies do not have common resonance frequencies and reconnection and resonant interaction is not possible.
  3. Does given harmony characterize given gene or the entire cell? All basic biomolecules associated with a gene would naturally correspond to the same harmony. If the rRNAs associated with ribosomes are in harmony mutually cellular harmony seems to be the only option. If ribosomes have their own harmonies, only certain ribosomes can translate given gene. This would bring in additional control tool. The most plausible picture is that the situation depends on what happens in the self-organization process. Some organs/organisms are more harmonious, others not so harmonious. Harmony need not be given fixed to remain the same: magnetic body can have motor actions changing the cyclotron frequencies. Moods could reflect the character of harmony at gene level.
  4. Does magnetic body control the differentiation by posing restrictions on gene expression or vice versa? The idea about magnetic body as intentional agent suggests that the first option is correct. There would be hierarchy of magnetic bodies with magnetic bodies at the higher level controlling bodies at the lower level. The value of Planck constant would label the hierarchy levels and also DNA codons would be characterized by "intelligence quotient" defined by heff/h. This would be nothing but the analog for the hierarchy of program modules and I have earlier considered the realization of this hierarchy.
  5. The selection of harmony could take place and be analogous to cell differentiation. This would be a self-organization process in which magnetic bodies of genes, cells, etc.. tune themselves to resonance with each other by modifying their magnetic fields by controlling their thickness (for monopoles flux the flux is invariant). Something analogous to the development of social skills. This could pose resonance as a constraint on processes like replication, transcription, reverse transcription, silencing, enhancing, editing, etc.... It might induce the differentiation at gene level.

    Editing processes for genome could be seen as being induced by the motor actions of the magnetic body involving reconnection and change of the value of heff changing the length of the flux tube and bringing biomolecules near to each other or separating them. This selection would also apply to the intronic part of DNA proposed to be responsible for topological quantum computation like processes. The copies of same fragment appearing in intronic portion and copies of genes could correspond to different harmonies.

It would be nice to identify some biological phenomenon difficult to understand in standard framework but having an elegant explanation in terms of magnetic body.
  1. The notion of harmony could manifest itself at the level of genes as different expressions for the copies of same gene if they correspond to different notions of harmony. The copies of gene are known as alleles. The alleles can indeed give rise to different phenotypic traits such as different pigmentation.
  2. Morphogenesis provides examples of this kind of phenomena (see this). The key idea is that DNA and cell replication is induced by the replication of magnetic bodies serving as information carriers. For instance, memory as behavioral patterns can be inherited by the piece of planaria worm not containing the brain. The explanation could be that the magnetic body carries behavioral patterns replicated in the splitting of the worm.
  3. Epigenetics studies changes of gene expression not caused by the change of DNA itself. Epigenome is the highly dynamic part of DNA controlling expression of the rather stable part of genome. One might regard stable part of genome as hardware and epigenome as topological quantum computer programs assignable to magnetic body and modifying gene expression epigenetically. Comment sign in computer code serves as a computer scientific metaphor for epigenetic control by repression.
The modelling of epigenesis in terms of magnetic body and bio-harmonies deserves a separate discussion.
  1. The modification of transcription rate is the basic tool of epigenetic regulation. There are two basic mechanisms involved. Histone modification affects the histones of chromatin so that the transcription is repressed or activated. Histone modification takes place by several mechanisms. DNA methylation occurs for CpG pair and if it occurs for a promoter region it represses the transcription and serves as a kind of gene lock. The degree of methylation serves as a measure for the effectiveness of repression. I do not know whether the locking is absolute at the level of single gene or whether only the transcription rate is reduced. Two mechanisms are mentioned in the Wikipedia article. Methylation can impede geometrically some step in the transcription. Methylated site can be also accompanied by proteins affecting histones in chromatin and in this manner impede transcription.

  2. The notions of magnetic body and bio-harmony suggest an alternative - one might even hope fundamental - mechanism of repression. Methylation (histone modification) could affect some cyclotron frequency associated with DNA codon (histone). In the optimal situation for transcription the DNA and protein catalyzing the transcription or mRNA are in resonance. When cyclotron resonance condition is not exactly satisfied, the reconnection rate for the U-shaped flux tubes associated with the molecules involved in the process is reduced and also transcription is repressed.

    I have considered also the radical possibility that the dynamics at the level of magnetic body is fundamental for biology and that magnetic body defines templates for the bio-molecular self-organization making dark matter dynamics visible. This is probably too extremist view and it would seem that biochemistry affects the cyclotron frequencies assignable to the magnetic body by affecting the strengths of magnetic fields also at dark magnetic flux tubes.

  3. The notions of epigenetic code and histone code have been proposed. Epigenetic code would consist of histone modifications and additional modifications such as DNA methylation. The codeword of the epigenetic code could code for some larger unit than protein: say gene or entire cell. The hypothesis is that the chromatin-DNA interactions are induced by histone tail modifications (such as methylation, acetylation, ADP-ribosylation, ubiquitination, citrullination, and phosphorylation). There are 4 histones and the position of modification varies as well as the modifier (the above modifications are not the only ones) so so that the number of modifications is very large.

    The addition of bioharmonies to the genetic information could simplify the situation dramatically since the modifications could be seen as defining of of the 256 bio-harmonies with 64 chords each (this for fixed scale which varies if the value of magnetic field strength is varied: biophoton spectrum in visible is proposed to represent the range of values of magnetic field). The most plausible starting hypothesis is that given harmony characterizes the gene. Much simpler option would be that the harmony characterizes entire cell or even group of cells.

    If the modification by kicking cyclotron frequency out of harmony is enough to repress transcription, almost endless number of bio-chemical manners to achieve would exist but the epigenetic code could be very simple at the basic level as TGD would predict. Each bio-harmony would provide a representation of genetic code in terms of 3-chords predicting correctly the DNA-amino-acid correspondence (there are actually two slightly differing codes explaining the presence of 21st and 22nd amino-acid and deviations from the standard code). The states of dark protons (or neutrons) are also proposed to realize genetic code: it is an open question whether these codes imply each other as they should.

  4. The understanding of transgenerational epigenetic inheritance raises difficult challenges. One should understand how histone modification and DNA methylation could be transferred in cellular division or inherited by the offspring. Transgenerational interaction of the genomes seems necessary. In TGD framework the interaction of magnetic bodies of via resonance mechanism could transfer the epigenetic programs to the offspring. Offspring could "learn" the epigenetic programs of the mother by tuning.
  5. Gregory Carey gives nice real life examples about the complexities of epigenesis identified quite generally as gene regulation (see this). He compares the gene regulation involved with the handling of a stressful situation to "nightmarish Rube Goldberg mousetrap" and sees the process as extremely ineffective from engineering point of view. For instance, the hormones secreted to blood circulation are distributed to the entire body. The whole thing could be carried out in brain! He also wonders why evolution is so inefficient. All cells have same genome although most of the genes are silenced. Second strand of DNA is totally un-used and most of DNA consists of introns. His explanation is that evolution does not make long term plans but finds just a solution to a particular without thinking it from a wider perspective: "If it ain't broke, don't fix it".

    I tend to see this differently. If entire body is coherent quantum entity, engineering based thinking does not make sense. Entire body and also magnetic body must be informed from the stress situation since the reaction is holistic. The genes which are not used for gene expression might be used for other purposes. Topological quantum computation could be this purpose in TGD framework and repressed genes could be thus used for quantum information processing. Information processing could be actually the dominating function of the DNA of higher vertebrates.

To sum up, magnetic body could be seen as the "boss" controlling the gene expression and also the evolution of genome in longer scales. Magnetic body would use bio-molecular mechanisms for its purposes. This would bring in a new kind of inheritance: bio-harmony would be inherited. The most spectacular almost-prediction would be that genetic code is many-to-one only in statistical sense.

For details see the chapter Three new physics realizations of the genetic code and the role of dark matter in bio-systems or the article Magnetic body, bio-harmonies, morphogenesis, and epigenetics.

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