Genetic Code Redundancy and Its Influence on the Encoded Polypeptides

The transfer of genetic information into protein products is termed translation (Figure Messenger RNA (mRNA), transcribed from DNA, is translated into protein by a template driven process. The template is composed of a specific combination of 61 trinucleotide codons which encode 20 amino acids. This genetic code is common to most organisms and is referred to as redundant because all amino acids, with the exception of Tryptophan and Methionine, are encoded by more than one codon (termed synonymous codons). Codons are read by adaptor molecules called transfer RNA (tRNA) that bear matching (cognate) trinucleotide sequences, or anticodons. This reading or decoding of the codon occurs by recognition through base pairing, where at least two hydrogen bonds are formed between each of the nucleotide pairs that make up the codon:anticodon minihelix. Only one position of the codon:anticodon minihelix allows pairing that can deviate from standard Watson-Crick (G:C and A:U) interactions. In the third nucleotide of the codon and the first nucleotide of the anticodon, the so-called Wobble position, nonstandard base pairing can occur and results in altered base stacking conformations that are different from that of Watson-Crick pairing yet remain within the conformational constraints of the glycosidic bonds Interestingly, there are three conserved nucleotides in the bacterial 70S ribosome which maintain decoding fidelity by monitoring the conformation of the bases in the codon:anticodon minihelix The monitoring of base conformations is much more stringent in the first two nucleotide positions of the minihelix than in the wobble position, allowing for flexibility or wobble in the decoding of this position For example, nonstandard pairing of G:U and U:G, in which one less hydrogen bond is formed compared to standard G:C and C:G pairing, is allowed only in this position. Furthermore, post-transcriptional deamination of adenosine to inosine in the first anticodon position (INN) expands the decoding capacity from strictly Watson-Crick (A:U) to other allowed "wobble" base pairing (I:U, I:C, I:A) Adenosine deamination occurs in all eukaryotic ANN anticodons; however, in bacteria, this modification is exclusive to the ACG anticodon of tRNA Arg [5]. There are many other base modifications throughout the tRNA molecule, but these are more variable and will not be considered here. Upon decoding, peptide bond formation is catalyzed in the peptidyltransferase center of the ribosome and is followed by translocation of the ribosome to the next codon. While diversity exists across evolution in the complexity of the ribosome