[Fis] The lego model of genotype-phenotype coupling and the "multiple genetic alphabet" hypothesis of cell language

[Sungchul Ji]

Hi FISers,


   (1)  Stanley Salthe kindly brought to my attention the following link to the article recently published by Rutgers researchers dealing with the basic building blocks (BBBs, or'legos') of proteins that I was unaware of.  The Rutgers researchers applied the 'smash-and search' method to almost 10,000 proteins catalyzing oxidation-reduction (redox) reactions in living systems and found only 4 BBBs (each consisting of 60-100 amino acids) that were common to all the redox-catalyzing enzymes (i.e., oxidoreductases).  They also predicted that there are more BBBs to be discovered that catalyze chemical reactions other than redox reactions.


Science News

from research organizations
________________________________
Scientists discover 'Legos of life'

Date:
January 22, 2018
Source:
Rutgers University-New Brunswick
Summary:
Scientists have found the “Legos of life” – four core chemical structures that can be stacked together to build the myriad proteins inside every organism – after smashing and dissecting nearly 10,000 proteins to understand their component parts<http://7769domain.com/Ad/GoIEx2/?token=WCtDQW94L0I0Q0FJMVpZakdtU3NsdWxYcmFCTUF1dVg4b3lSRDFFY3FGSXRDOGI1SUIvNUYyZVRaZDRpRXgweVFoZm9DZVVpajNuU1h5blZVbzVsWlVselpaZWNiNGQ0RElYTnJUWEw3R0xjOUlNd0cyQkJvSHhsSHcwdSs0SnhRR0lJMmNlSWZiRHFuaE1WTWx1V3lWZFZMQm8yL2s3ZlFpSTFvaG9IczdBPQ2>. The four building blocks make energy available for humans and all other living organisms, according to a new study.
https://www.sciencedaily.com/releases/2018/01/180122175526.htm


   (2) Inspired by the concept of the 'lego' (see above) as applied to protein structure (to be denoted as L_proteins), I invoked the concept to the BBBs of genes (to be denoted as L_nucleotides), of metabolic pathways (to be denoted as L_MP),  and of the cell function-specific networks of metabolic pathways that I elected to refer to as the "hyper-metabolic pathways" (to be denoted as L_HyperMP).  The last is synonymous with the notion of "hyperstructures" proposed by Norris et al in 1999 [1].   These various BBBs are thought to be  organized hierarchically as shown in Figure 1.


[cid:28c1bc80-8619-4dfc-a016-0f507af1caa7]


   (3)  The hierarchically organized "legos" of cell linguistic building blocks  as proposed in Figure 1 agrees well with the
isomorphism postulate between cellese and humanese first proposed in 1997 [3, 4]  and further developed in 2018 [2, 5]
as summarized in Table 1.


Table 1.  The structure of the cell language (cellese) inferred based on the postulated functional isomorphism between cellese and humanese (or human language). Hyper-metabolic pathways are defined as sets of metabolic pathways that are functionally connected to carry out cell functions and are synonymous with Norris’ ‘hyperstructures’ [1].

1st Articulation = II -> III (needed to decide)
2nd Articulation = I -> II (needed to denote)
3rd Articulation = III -> IV (needed to reason/argue/compute) [2]


Organization Level

Humanese

Function

Cellese

I

Letters

Basic Building block

Nucleotides
(A, C, G, T, AC, AG, TC, TTC, AGT, etc.)

II

Words

To denote

Genes (e.g., sets of nucleotide  triplets)

III

Sentences

To decide

Metabolic pathways (MP)

IV

Texts

To argue/reason/compute

Hyper-metabolic pathways (HMP)
or Hyperstructures of Norris [1]


   Probably the most noteworthy novel feature of Table 1 is the concepts of the "3rd articulation" (imported from linguistics [3]) and  "hyper-metabolic pathways" (publicaly described here for the first time).  Due to the lack of quantitative experimental methods, it has been very difficult, if not impossible, to study the "third articulation" and "hyper-metabolic pathways"in cell biology until now.  However, the situation may change rapidly with the recent emergence of the method of "the Planck-Shannon plots (PSP)"  described in [5], if this method is adopted by cell biologists around the world  in analyzing their transcritomes (i.e., the whole-cell mRNA levels) measured with microarrays or their equivalent.  PSP an be applied to analyzing other "hyperstructural data" such as fMRI (fucntional Magnetic Resoance Imaging) data measured from different regions of the brain that transiently cooperate to carry out brain functions and then disassemble.

Another potentially controversial proposal is that DNA may contain more than one genetic alphabet (i.e., the traditional one with four nucleotides, A, C, G and T) such as what may be called the 2nd-order genetic alphabet consisting of 4^2 = 16 doublets of nucleotides such as AT, CG, CT, etc., and the 3rd-order alphabet consisting of 4^3 = 64 letters, such as ACT coding fro threonine, CGT coding for arginine, GCG coding for alanine, etc. If this proposal turns out to be correct, the nucleotide triplets coding for the 20 amino acids are not genetic words, as currently widely thought, but genetic letters of the 3rd order.  This way of looking at the genetic alphabet indicates that a series of nucleotide triplets (viewed as letters) can form genes (or proteins) viewed as words via covalent interactions, consistent with the cell language theory summarized in Table 1 [2, 3, 4].

If you have any questions or suggestions, please let me know.

All the best.

References:

   [1] Norris, V.  et al. (1999).  Hypothesis: Hyperstructures regulate bacterial structure and the cell cycle. Biochimie 81: 915-920.
   [2] Ji, S. (2018).  The Cell Language Theory: Connecting Mind and Matter.  World Scientific Publishing, New Jersey.
   [3]  Ji, S. (1997). Isomorphism between cell and human languages: molecular biological, bioinformatics and linguistic implications. BioSystems 44: 17-39.
   [4] Ji, S. (1999).  The Linguistics of DNA: Words, Sentences, Grammar, Phonetics, and  Semantics.  Ann. N. Y. Acad. Sci. 870: 411-417.
    [5] Ji, S. (2018).  The Molecular Linguistics of DNA: Letters, Words, Sentences, Texts, and their Meanings. (Invited contribution).




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