Genetic information can be mapped in a simple schematic of the molecular sets during protein synthesis. The state-of-art method used today is quite simple. Nucleotide sequences provide information that is translated directly into amino acid sequences, and nothing else.
The diagram shows that three nucleotides translate into one amino acid. This model teaches that the codon is the only salient unit of information contained in polynucleotides during translation, where a codon is a grouping of three nucleotides specifying one and only one amino acid in a polypeptide chain. If this is taken as the complete foundation of genetic information, then the schematic is fairly simple, and the method of mapping seems trivial:
1. Map all possible codons with amino acids.
Of course this has already been done, and this is the conventional view of genetic translation today. Unfortunately, this view is technically incomplete, and there are many observed phenomena that cannot be easily handled by this model. No attention is given in this view to the specific parameters of a peptide bond when it is formed. No role is given to any of the RNA sets - mRNA, tRNA, rRNA - in forming the specific parameters of each peptide bond, beyond determining the two residues that will bond together. The specific conformation of these two residues as an immediate consequence of their formation is being completely ignored. Do we know for certain that this is a wise and accurate view of translation?
Do all nucleotide sequences and apparati that bond the same two amino acids lead to identical peptide bonds? In other words, given the 36 codon pairs (147,456 possible genons) that can create a leucine-arginine peptide bond, does this bond emerge from translation in identical conformations in all cases. If not, this constitutes real genetic information, regardless of the impact, if any, it might have post-translation. The empiric evidence is accumulating evermore rapidly that silent mutations can change peptide bond conformations in the folded protein. Now the really important question is whether or not silent mutations can change bond conformations at the moment of translation.
I say they can.
Rafiki's method of mapping holds that the peptide bond is the primary output of translation. Amino acid sequences are a necessary consequence of peptide bonding, as opposed to the commonly held reverse viewpoint that peptide bonds are a trivial, yet necessary consequence of amino acid sequencing. Look at the basic picture of a peptide group:
This is the fundamental output of translation. It includes all of the informative parameters of the peptide bond: residue identities, major configuration - cis or trans - and phi-psi angles. The key question for genetic translation is, How many distinct peptide groups can be formed during translation? If all peptide bonds are identical when they form, then the answer is 400 (20 amino acids X 20 amino acids). If some residue pairs form distinct peptide conformations within different sequence contexts, then the answer is >400, and the genetic code can no longer have only one degree of freedom in translation.
I prefer to view the primary structure of a polypeptide - the immediate output of translation - as an overlapping sequence of peptide groups, not a sequence of amino acids. The sequential identities of amino acids are but components of the distinct identities of sequential peptide groups.
Some new terms will be added to the old ones and applied to the new method of mapping genetic information:
Genon – the unit of mRNA involved in fully describing a single peptide
Pepton – the ensemble of tRNA involved in fully describing a peptide bond.
Whereas the linear model is flat, requiring knowledge of isolated codon correlations alone to determine primary sequence, the new model is hierarchical, requiring a number of elements for determination of the primary structure of a polypeptide backbone. The concepts of genon and pepton are valid even in the classic model, but they would have little use in that one-codon-one-amino acid world. The new method of mapping is still conceptually simple, but new steps must be added.
1. Map all expressed tRNA to amino acids in an organism.
2. Map all possible genons to peptons.
3. Map all peptons to peptide bonds.
The above schematic is modified to reflect this new method.
C = Codon . . T = tRNA . . PB = Peptide Bond . . AA = Amino Acid
The most significant result is that the peptide bond becomes the focal point of the genetic code. The genetic code is composed of at least two forms of RNA, mRNA and tRNA, and it is an overlapping code; therefore, no unit of information can be removed from its appropriate level of context yet still retain its complete meaning. Each tRNA, and therefore the amino acid it carries, plays a role in two peptide bonds, so a single substitution might impact the output in more than one way. It is entirely plausible that the state of leading and following bonds will effect the ultimate conformation of any given bond. The schematic illustrates this by including the surrounding tRNA in the concept of a pepton.
This method should be universal, but the results are not necessarily universal. In other words, it must be applied to each organism under study, and it is expected to yield different results for each. Every organism expresses a different population of tRNA molecules, and each codon has the ability to specify more than one tRNA. This is in stark contrast to the one-codon-one-amino acid view of the genetic code. Therefore, it is only within a genon context that codon-tRNA mappings are made.
It is not guaranteed that every organism will share the same view of genons and peptons, just as they are known to differ on approaches to codons. It has been shown that organisms have the ability to change their codon to amino acid correlations, and they even have the ability to eliminate codons entirely from their code (codon capture). An organism with a missing codon cannot have the same code as one without a missing codon. So even the number of codons is not a universal part of the code. Likewise, it should be expected that an organism might take advantage of flexibility in genon and pepton mechanisms. Number and type of each can be expected to vary. It may even be found that genons and peptons vary in size within and between organisms. For this reason it is not possible to precisely define sizes and varieties of these genetic components without data.
There is a transition from the monotony of bonds in DNA to the diversity of bonds in protein. This is literally a translation of genetic information. The $64,000 question is, how is this transition governed? The process of making a total bond identity has traditionally been believed to occur post-translation, but this is a dangerous, unproven assumption. Our new method of mapping brings to light the need to track bond conformations all the way to the mechanisms of bond formation, if only for the sake of intellectual accuracy and completeness.
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