Source: Genetic code and Amino Acid Translation

Well, folks, someone has been listening to me about the importance of the Inosine and Xanthine families.

The graph and charts of the Amino Acid Codons and Anti-Codon Wobble Pairing rules with the inosine family has been admirably put into print, much better than I could format it, but nevertheless, it shows Inosine = I in the anti-codon columns occurs 8 or 9 depending on the glycine controversy which has never been definitively settled.

Nevertheless, the current genetic code does “hedge its bets”  by having synonymous codes i.e. having the first two codons the same, but varying the third column of the 21 amino acids. You will note in most instances, that Inosine wins in most cases, by measuring frequency of use by the tRNA gene in synthesizing the peptide bond and anti-codon binding amino acid. 9/21 = 3/7 = 42.85% of being selected in the third column.

I think we have done it. Now to test and validate. Please help me, I am not a bioinformatic wizard like many of you 14,000+ colleagues, especially in in-silico modeling. To be honest, I have not found a way around the current method  to directly locate A to I mRNA post transcriptional edits without the AG proxy.

Currently, certain AG anti-codons are used as proxies for validated AI mRNA editing sites; the error is assuming the translation machinery, the next step in protein synthesis translates the final mRNA transcript as G uanosine and not Inosine.This is clearly wrong, from nature’s perspective.

The current sequencers have only 4 choices (AUGC= RNA code) in the coding scheme. It is inevitable G will replace I = Inosine since the sequencing machine has no Inosine code available.  Common sense tells us G = NH2 + CO is not the same as Inosine = CO. And, a second error is naming  Inosine as an analogue of Guanosine. They are clearly separate purine nucleotides, nucleosides and purine bases.

The extra NH2 of Guanosine makes a significant difference in the translational outcome, having an extra NH2 in the translated amino acid produces the wrong amino acid. The C=O makes water, NH2 makes NH3, ammonia, which is very toxic in the human body, especially the CNS and liver.

Another “scratching the head logic” in the central dogma coding schema, is the presence of the Inosine and Xanthine enzymes:  IMPDH1,2 ; HGPRT, Xanthine Oxidase and Dehydrogenase, Inosine Kinase, PNP, cIMP, and many other enzymes just being discovered. My question is, if Inosine is replaced by Guanosine in the Translational phase of amino acid/protein synthesis, how are there any Inosine or Xanthosine enzymes? If Inosine is not processed by the ribosomal/ribozyme in translation, how are there any inosine/xanthine proteins down stream and down process?

I donot have the means to expand the reading,sequencing/decoding   capabilities of the high throughput sequencers to process and visualize the inosine and xanthine codes. It will take “one of the big boys” like Illumina,  to modify their machines to differentiate more than 4 codes in a single parallel read. The sequencing machine should have at least 6 or 7 codes to correctly identify the complete set of nucleotides found in the human genome. After all if only 3% of the 3.2 billion base pair sequences code for proteins, what do the other 97% of the nucleotide base pair code for?

It has been commonly accepted that 90-95%  of all cells, undergo some type of mRNA transcriptional editing, and Adenosine to Inosine is by far the most frequent editing and alternative splicing type;  this suggests, as more research is forthcoming, the inosine/xanthine families will be found to play a much bigger role in the genetic and epigenetic events and processes throughout the human genome.

Everyone, please reprogram your computers to duplicate the chart linked in the purple hyperlink, called Genetic Code and Amino Acid Translation. The 8/9 new Inosine anti-codon amino acids: (Alanine, Leucine, Serine, Threonine, Valine, Isoleucine, Arginine, Proline and Glycine); are many of the same amino acids found in the Heptad Alpha helix, the first and still most common protein motif found in nature today. The leucine zipper, serine/threonine kinase phosphorylation, and the proline kink, are a few of the more prominent functions of the Inosine Wobble Amino Acids.

These 8/9 amino acids are also the most frequent ones found in the “A” and “D” hydrophobic cores in the heptad alpha helix coiled coil structures, which are literally the anchoring forces binding proteins together at the highest order quarternary protein helices which underpin the most complex and sophisticated functions found in the human body, from pluripotent stem cells to human consciousness and the executive functions of the neocortex.