The Invention of Proteomic Code and mRNA Assisted Protein Folding

REVIEW

The Invention of Proteomic Code and mRNA Assisted Protein Folding.

by

Jan C. Biro

Homulus Foundation, 612 S Flower St. #1220, 90017 CA, USA. jan.biro@att.net

Keywords:

Gene, code, codon, translation, wobble-base,

Abbreviations (excluding standard abbreviations:

2 Abstract

Background The theoretical requirements for a genetic code were well defined and modeled by George Gamow and Francis Crick in the 50-es. Their models failed. However the valid Genetic Code, provided by Nirenberg and Matthaei in 1961, ignores many theoretical requirements for a perfect Code. Something is simply missing from the canonical Code.

Results The 3x redundancy of the Genetic code is usually explained as a necessity to increase the resistance of the mutation resistance of the genetic information. However it has many additional roles. 1.) It has a periodical structure which corresponds to the physico-chemical and structural properties of amino acids. 2.) It provides physico-chemical definition of codon boundaries. 3.) It defines a code for amino acid co-locations (interactions) in the coded proteins. 4.) It regulates, through wobble bases the free folding energy (and structure) of mRNAs. I shortly review the history of the Genetic Code as well as my own published observations to provide a novel, original explanation of its redundancy.

Conclusions The redundant Genetic Code contains biological information which is additional to the 64/20 definition of amino acids. This additional information is used to define the 3D structure of coding nucleic acids as well as the coded proteins and it is called the Proteomic Code and mRNA Assisted Protein Folding.

3 Introduction

Mapping between messages in nucleic acid and protein alphabet is a fascinating story, a story that still unfolding. It is about to understand the rules of information transfer between DNA and proteins. First of all it is not only a biochemical puzzle and much of the early methods for devising codes came from combinatorics, information theory. Four and 20 (number of bases and amino acids) seems to be magical numbers with amazingly many possible mathematical connections between them [1].
The existence of a Genetic Code became obvious immediately after the discovery of DNA structure [2, 3]. The first suggestion for a code came from George Gamow, not even a biologist, but a physicist who became most famous as the chief proponent of the Big Bang theory in cosmology. He proposed a Diamond Code [4-6] where DNA acted directly as a template for assembling amino acids into proteins. Various combinations of bases along one of the grooves in the double helix could form distinctively shaped cavities into which the side chains of amino acids might fit. Each cavity would attract a specific amino acid; when all the amino acids were lined up in the correct order along the groove, an enzyme would come along to polymerize them. Gamow’s code turned out to be an overlapping triplet code which provided exactly the desired 20 combinations. There are many beautiful aspects of the overlapping codon: a) it maximizes the density of information storage and b) even though three bases are needed to specify any single amino acids, the overall ratio of bases to amino acids approaches 1:1; c) it supposes that the distance between base pairs in DNA and the distance between amino acids in the proteins is raptly similar, which is exactly the case; 4) and avoids the possibility and consequences of frame shift. Unfortunately this code has serious constrains: only 44 = 256 overlapping codon combinations are possible, while with 20 kinds of amino acids, there are 202 = 400 possible dipeptides. The 144 “impossible” dipeptides were found in real proteins by Sidney Brenner [7] and it ruled out Gamow’s codon “diamonds”.
Another brilliant code was created by Francis Crick [8] the Comma-Free Code. Crick was speculating about an adaptor hypothesis (that he never published) the idea that amino acids do not interact directly with mRNA, but there is a mediator which recognizes the codons. Codons line up continuously along the DNA, like pearls on a neckless, and are recognized by a specific mediator. (This mediator is known today as tRNA). However, unlike a neckless, there is no space (“comma”) between the codons which would indicate the codon boundaries. How is it still possible to distinguish between meaningful (those necessary 20 which lined up prettily on the DNA) and meaningless (the remaining 44 overlapping) codons? The answer was original: there is no mediator for meaningless codons. This solution was so simple and elegant, that it got the name the “prettiest wrong idea in all of 20th-century science”.

There were many theoreticians involved in the invention of the Genetic Code. A common future of all th

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