Genetic code

Translation is accomplished by the ribosome, which links proteinogenic amino acids in an order specified by messenger RNA (mRNA), using transfer RNA (tRNA) molecules to carry amino acids and to read the mRNA three nucleotides at a time.

[2] Soviet-American physicist George Gamow was the first to give a workable scheme for protein synthesis from DNA.

[5] In 1954, Gamow created an informal scientific organisation the RNA Tie Club, as suggested by Watson, for scientists of different persuasions who were interested in how proteins were synthesised from genes.

Crick presented a type-written paper titled "On Degenerate Templates and the Adaptor Hypothesis: A Note for the RNA Tie Club"[9] to the members of the club in January 1955, which "totally changed the way we thought about protein synthesis", as Watson recalled.

[11] The Crick, Brenner, Barnett and Watts-Tobin experiment first demonstrated that codons consist of three DNA bases.

[12] They used a cell-free system to translate a poly-uracil RNA sequence (i.e., UUUUU...) and discovered that the polypeptide that they had synthesized consisted of only the amino acid phenylalanine.

[16] Extending this work, Nirenberg and Philip Leder revealed the code's triplet nature and deciphered its codons.

In these experiments, various combinations of mRNA were passed through a filter that contained ribosomes, the components of cells that translate RNA into protein.

Even models are proposed that predict "entry points" for synthetic amino acid invasion of the genetic code.

[24] In 2015 N. Budisa, D. Söll and co-workers reported the full substitution of all 20,899 tryptophan residues (UGG codons) with unnatural thienopyrrole-alanine in the genetic code of the bacterium Escherichia coli.

[26][27] In 2017, researchers in South Korea reported that they had engineered a mouse with an extended genetic code that can produce proteins with unnatural amino acids.

The most common start codon is AUG, which is read as methionine or as formylmethionine (in bacteria, mitochondria, and plastids).

[33] The three stop codons have names: UAG is amber, UGA is opal (sometimes also called umber), and UAA is ochre.

These errors, mutations, can affect an organism's phenotype, especially if they occur within the protein coding sequence of a gene.

These mutations usually result in a completely different translation from the original, and likely cause a stop codon to be read, which truncates the protein.

[47] In large populations of asexually reproducing organisms, for example, E. coli, multiple beneficial mutations may co-occur.

For example, the amino acid leucine is specified by YUR or CUN (UUA, UUG, CUU, CUC, CUA, or CUG) codons (difference in the first or third position indicated using IUPAC notation), while the amino acid serine is specified by UCN or AGY (UCA, UCG, UCC, UCU, AGU, or AGC) codons (difference in the first, second, or third position).

[49] A practical consequence of redundancy is that errors in the third position of the triplet codon cause only a silent mutation or an error that would not affect the protein because the hydrophilicity or hydrophobicity is maintained by equivalent substitution of amino acids; for example, a codon of NUN (where N = any nucleotide) tends to code for hydrophobic amino acids.

The genetic code is so well-structured for hydropathicity that a mathematical analysis (Singular Value Decomposition) of 12 variables (4 nucleotides x 3 positions) yields a remarkable correlation (C = 0.95) for predicting the hydropathicity of the encoded amino acid directly from the triplet nucleotide sequence, without translation.

[53] In some proteins, non-standard amino acids are substituted for standard stop codons, depending on associated signal sequences in the messenger RNA.

[60] Surprisingly, variations in the interpretation of the genetic code exist also in human nuclear-encoded genes: In 2016, researchers studying the translation of malate dehydrogenase found that in about 4% of the mRNAs encoding this enzyme the stop codon is naturally used to encode the amino acids tryptophan and arginine.

[66] This type of recoding is induced by a high-readthrough stop codon context[67] and it is referred to as functional translational readthrough.

[69] The most extreme variations occur in certain ciliates where the meaning of stop codons depends on their position within mRNA.

When close to the 3' end they act as terminators while in internal positions they either code for amino acids as in Condylostoma magnum[70] or trigger ribosomal frameshifting as in Euplotes.

For example, the program FACIL infers a genetic code by searching which amino acids in homologous protein domains are most often aligned to every codon.

[57] As of January 2022, the most complete survey of genetic codes is done by Shulgina and Eddy, who screened 250,000 prokaryotic genomes using their Codetta tool.

Despite the NCBI already providing 27 translation tables, the authors were able to find new 5 genetic code variations (corroborated by tRNA mutations) and correct several misattributions.

[80] A hypothetical randomly evolved genetic code further motivates a biochemical or evolutionary model for its origin.

A series of codons in part of a messenger RNA (mRNA) molecule. Each codon consists of three nucleotides , usually corresponding to a single amino acid . The nucleotides are abbreviated with the letters A, U, G and C. This is mRNA, which uses U ( uracil ). DNA uses T ( thymine ) instead. This mRNA molecule will instruct a ribosome to synthesize a protein according to this code.
The genetic code
Reading frames in the DNA sequence of a region of the human mitochondrial genome coding for the genes MT-ATP8 and MT-ATP6 (in black: positions 8,525 to 8,580 in the sequence accession NC_012920 [ 31 ] ). There are three possible reading frames in the 5' → 3' forward direction, starting on the first (+1), second (+2) and third position (+3). For each codon (square brackets), the amino acid is given by the vertebrate mitochondrial code , either in the +1 frame for MT-ATP8 (in red) or in the +3 frame for MT-ATP6 (in blue). The MT-ATP8 genes terminates with the TAG stop codon (red dot) in the +1 frame. The MT-ATP6 gene starts with the ATG codon (blue circle for the M amino acid) in the +3 frame.
Examples of notable mutations that can occur in humans [ 35 ]
Grouping of codons by amino acid residue molar volume and hydropathicity . A more detailed version is available.
Axes 1, 2, 3 are the first, second, and third positions in the codon. The 20 amino acids and stop codons (X) are shown in single letter code .
Genetic code logo of the Globobulimina pseudospinescens mitochondrial genome by FACIL. The program is able to correctly infer that the Protozoan Mitochondrial Code is in use. [ 57 ] The logo shows the 64 codons from left to right, predicted alternatives in red (relative to the standard genetic code). Red line: stop codons. The height of each amino acid in the stack shows how often it is aligned to the codon in homologous protein domains. The stack height indicates the support for the prediction.
Unspecified L-amino acid