Wednesday, March 19, 2008

TGD based model for the evolution of genetic code: II

The net is wonderful. Yesterday evening I decided to search for articles about the possible role of dinucleotides in prebiotic evolution. "Dinucleotide" as a search word gave something about NADH and the only thing I understood that this is not relevant. Then I decided to be very optimistic and use as search words "dinucleotide" "prebiotic" simultaneously. To my surprise I found two gems which guaranteed that I did not sleep too much during the last night!

The first gem did not relate to dinucleotides in a direct manner but I learned that the attempts to synthesize RNA sequences from nucleotides lead to 2',5' form of RNA: recall that the production of 3',5' RNA sequences has not been successful, only single nucleotides have been produced (see the article Experimental Testing of Theories of an Early RNA World by A. D. Ellington). This fits completely with the cautious hypothesis that RNA1 indeed corresponds to 2',5' form of RNA consisting of A,G,U,I and that ordinary 3',5' RNA, which I call RNA2, emerged as dinucleotides, which can polymerize to longer sequences and that this process was catalyzed by aminoacids.

Second gem was directly related to dinucleotides, prebiotics, and genetic code. Somewhat disappointingly, I am not the only person who has considered the idea of 2-code. The title of the paper by S.D. Copley. E. Smith and H. J. Morowitz was A mechanism for the association of aminoacids with their codons and the origin of the genetic code. To very briefly summarize the content of the paper (I am of course not chemist and I see the paper from by "biomolecules connected by magnetic flux tubes" perspective so that it is easy to ridicule me).

  1. The paper suggests that there was prebiotic code in which 2-codons formed by dinucleotides of RNA define the prebiotic code. The paper starts from facts well-known to biochemists (I wish I were a biochemist, really). The first nucleotide X of the dinucleotide XY assigns to XY one of the four simple precursors of aminoacids. The correspondence is

    C,A,U,G → α-keto glutarate (α-KG), oxaloacetate (OAA), pyruvate, α-keto acid.

    Ketone means a compound with a generic formula R1-(CO)-R2, where CO has double valence bond. For α-keto acid R1 is replaced with O-(CO) group.

    These letter sequences tell to the typical reader probably as little as they tell to me (I am doing the ridicule myself!). If prebiotic code would be like the usual code the code would map 16 dinucleotides to 4 precursors.

  2. It is the reaction pathway leading to the aminoacid rather than molecule, which is coded. This is new! We have move to a higher level of abstraction! The empirical observation is that second nucleotide Y of XY correlates very strongly with how hydrophobic the aminoacid is. Y= U corresponds to maximal hydrophobia and its conjugate Y=A to maximal hydrophily. Y= G and C are in between. At deeper level Y together with X determines which reaction pathway way leading from the precursor to the aminoacid is selected.

  3. Authors propose that this correspondence means that dinucleotides XY form covalent bonds with precursors and this bonding catalysis the reaction leading to the aminoacid. For obvious reasons I do not have strong opinions about this.

Consider now the interpretation of the results in TGD framework.

The coding of the reaction pathway would be in terms of braid strands. The two ("wormhole") magnetic flux tubes beginning from the X and Y would end up to the precursor. The quark u,d or antiquark uc, dc labeling X would tell which precursor the magnetic flux tube ends at. What is the rule involved? What property of nucleotide X and precursor fixes the correspondence characterizing reaction pathway? It certainly seems that the flux tube connects X to a catalytic "hot spot" since X and this hot spot must end up near to each other in the phase transition reducing Planck constant and thus length of the magnetic flux tube. The charges possibly assignable with the hot spots - what ever they are - is a good guess but there is more involved.

It seems that the nucleotides of codon are like 4-digits with first digits having the highest significance. The division of dinucleotide XY to two nucleotides should correspond to a similar division UV of the precursor to two parts. U would change in the reaction in the same manner for all aminoacids resulting from a given precursor but the change should depend on X. One can identify at U as a portion at the right end of the precursor (see the article). The left end of precursor would in turn connect with Y.

  1. To get some idea one an start from the formation of flux tubes between DNA nucleotides and their conjugates and hope that something very similar happens as flux tubes are formed between RNA dinucleotides and precursor structures. The electromagnetic charge Qem(X) of the quark associated with nucleotide X should correlate with some property of the nucleotide, or rather the reaction pathway associated with the formation of the pair formed by nucleotide and its conjugate. Hydrogen bonds obviously characterize this pathway. Quark charge indeed correlates with the number of hydrogen bonds of the base pair: 3Qem+1= n(bonds). The sign of the quark charge in turn correlates with the direction of the hydrogen bonds.

  2. One might hope that also in the recent case the catalysis involves the formation of hydrogen bonds between dinucleotide and precursor structure. Authors suggest covalent bond and the appearance of double bonded oxygens in precursors does not leave much doubts. The reactions could however involve a co-catalyst forming hydrogen bonds with XY and covalent bonds with the precursor. Obviously also the co-catalyst should have UV type structure.

  3. One can ask whether the co-catalyst could behave effectively like the conjugate of the RNA dinucleotide for the reaction considered. If so, one could understand the selection of the reaction pathway, and the strategy would be to find simple bio-molecules which behave like RNA dinucleotides in this sense. The strongest and probably unrealistic assumption would be that NH2-N-O and O-NH-NH2 portions corresponding to A-T type hydrogen bonds and O-NH and NH2-N portions correspond to G-C type hydrogen bonds. Needless to say, neither the precursors nor aminoacids have this kind of portions: actually the precursors assigned to U,A,C contain only carbon and double-bonded O.

  4. There could be a close connection with hydrogen bonds and magnetic flux tubes defining braid strands. I have already earlier proposed that hydrogen bonds might involve new physics, in particular the fractionization of electron and proton charge. This led to the notion of N-atom with the idea being that the fractionization of em charge leads to the emergence of symbolic dynamics in the sense that molecules forming hydrogen bonds between each other correspond to fractional charges for electron or proton summing up to the standard charge. These conjugate charges would define name and "co-name" and these names would be more important for the dynamics than the details of the ordinary chemistry just as names are for the development (or non-development - as you wish) of theoretical physics;-). Half-hydrogen bond and its conjugate would also bring in "sex" at the molecular level. It remains a future challenge to see whether the notion of N-atom and braid concept can be fused together.

An ideal experimentalist with infinite brilliance and funding resources and enjoying endless trust of decision makers might be interested in carrying out the following experiments.

  1. Test whether RNA dinucleotides catalyze the transformation of the precursors (or something more complex behaving like RNA dinucleotide as far hydrogen bonding is involved) to aminoacids. In particular, test whether it is RNA1 or RNA2, which catalyzes the transformation of precursors to aminoacids.

  2. Suppose that one has a prebiotic soup containing 4 precursors of aminoacids and some concentration of dinucleotides of RNA1 or RNA2. Suppose that this indeed leads to the formation of aminoacids. If these aminoacids still possess the braid connections with nucleotides, the aminoacids in turn could catalyze the formation of further dinucleotides as suggested in the previous posting and RNA era could begin. It might be worth of checking also this.

  3. If this works then one has only the problem would be the generation of the seed dinucleotides. 2',5' RNA sequences are produced in the primordial situation but the sequences of 3',5' RNA are not in absence of catalyst or template. Primordial evolution should have resolved this problem in some very elegant manner.
    1. It is known that Na-montmorillonate, which is a clay mineral appearing in volcanic ash, catalyses a mixture of both 2'5' and 3'5' RNA dinucleotides, which are also dominantly L-L or D-D (see this). This solution looks fairly reasonable.
    2. The generation of aminoacids from precursors would be most naturally catalyzed by RNA1 dinucleotides. Is it too much to hope that this process is not catalysis in the precise sense of the word but transforms RNA1 dinucleotides to RNA2 dinucleotides?! If so, primordial evolution could be initiated in laboratory! Check also this!
    3. Speaking more seriously, a process transforming RNA1 to RNA2 would be enough. 2',5' RNA appears in peach latent mosaic viroid DNA (see this), and there should exist a process transforming 3',5' RNA to 2',5' RNA and vice versa. One might hope that the mechanism is simple enough to be realized primordially.

For details see previous posting and the chapter Prebiotic Evolution in Many-Sheeted Space-time of "Genes and Memes".


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