Genetic code

Last updated

The genetic code is the set of rules used by living cells to translate information encoded within genetic material (DNA or mRNA sequences of nucleotide triplets, or codons) into proteins. 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. The genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries.


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. RNA-codon.png
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 codons specify which amino acid will be added next during protein synthesis. With some exceptions, [1] a three-nucleotide codon in a nucleic acid sequence specifies a single amino acid. The vast majority of genes are encoded with a single scheme (see the RNA codon table). That scheme is often referred to as the canonical or standard genetic code, or simply the genetic code, though variant codes (such as in mitochondria) exist.


The genetic code GeneticCode21-version-2.svg
The genetic code

Efforts to understand how proteins are encoded began after DNA's structure was discovered in 1953. George Gamow postulated that sets of three bases must be employed to encode the 20 standard amino acids used by living cells to build proteins, which would allow a maximum of 43= 64 amino acids. [2]


The Crick, Brenner, Barnett and Watts-Tobin experiment first demonstrated that codons consist of three DNA bases. Marshall Nirenberg and Heinrich J. Matthaei were the first to reveal the nature of a codon in 1961. [3]

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. [4] They thereby deduced that the codon UUU specified the amino acid phenylalanine.

This was followed by experiments in Severo Ochoa's laboratory that demonstrated that the poly-adenine RNA sequence (AAAAA...) coded for the polypeptide poly-lysine [5] and that the poly-cytosine RNA sequence (CCCCC...) coded for the polypeptide poly-proline. [6] Therefore, the codon AAA specified the amino acid lysine, and the codon CCC specified the amino acid proline. Using various copolymers most of the remaining codons were then determined.

Subsequent work by Har Gobind Khorana identified the rest of the genetic code. Shortly thereafter, Robert W. Holley determined the structure of transfer RNA (tRNA), the adapter molecule that facilitates the process of translating RNA into protein. This work was based upon Ochoa's earlier studies, yielding the latter the Nobel Prize in Physiology or Medicine in 1959 for work on the enzymology of RNA synthesis. [7]

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. Unique triplets promoted the binding of specific tRNAs to the ribosome. Leder and Nirenberg were able to determine the sequences of 54 out of 64 codons in their experiments. [8] Khorana, Holley and Nirenberg received the 1968 Nobel for their work. [9]

The three stop codons were named by discoverers Richard Epstein and Charles Steinberg. "Amber" was named after their friend Harris Bernstein, whose last name means "amber" in German. [10] The other two stop codons were named "ochre" and "opal" in order to keep the "color names" theme.

Expanded genetic codes (synthetic biology)

In a broad academic audience, the concept of the evolution of the genetic code from the original and ambiguous genetic code to a well-defined ("frozen") code with the repertoire of 20 (+2) canonical amino acids is widely accepted. [11] However, there are different opinions, concepts, approaches and ideas, which is the best way to change it experimentally. Even models are proposed that predict "entry points" for synthetic amino acid invasion of the genetic code. [12]

Since 2001, 40 non-natural amino acids have been added into protein by creating a unique codon (recoding) and a corresponding transfer-RNA:aminoacyl – tRNA-synthetase pair to encode it with diverse physicochemical and biological properties in order to be used as a tool to exploring protein structure and function or to create novel or enhanced proteins. [13] [14]

H. Murakami and M. Sisido extended some codons to have four and five bases. Steven A. Benner constructed a functional 65th (in vivo) codon. [15]

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. [16]

In 2016 the first stable semisynthetic organism was created. It was a (single cell) bacterium with two synthetic bases (called X and Y). The bases survived cell division. [17] [18]

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. [19]

In May 2019, researchers, in a milestone effort, reported the creation of a new synthetic (possibly artificial) form of viable life, a variant of the bacteria Escherichia coli , by reducing the natural number of 64 codons in the bacterial genome to 59 codons instead, in order to encode 20 amino acids. [20] [21]


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 ). 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. Homo sapiens-mtDNA~NC 012920-ATP8+ATP6 Overlap.svg
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 ). 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.

Reading frame

A reading frame is defined by the initial triplet of nucleotides from which translation starts. It sets the frame for a run of successive, non-overlapping codons, which is known as an "open reading frame" (ORF). For example, the string 5'-AAATGAACG-3' (see figure), if read from the first position, contains the codons AAA, TGA, and ACG ; if read from the second position, it contains the codons AAT and GAA ; and if read from the third position, it contains the codons ATG and AAC. Every sequence can, thus, be read in its 5' → 3' direction in three reading frames, each producing a possibly distinct amino acid sequence: in the given example, Lys (K)-Trp (W)-Thr (T), Asn (N)-Glu (E), or Met (M)-Asn (N), respectively (when translating with the vertebrate mitochondrial code). When DNA is double-stranded, six possible reading frames are defined, three in the forward orientation on one strand and three reverse on the opposite strand. [23] :330 Protein-coding frames are defined by a start codon, usually the first AUG (ATG) codon in the RNA (DNA) sequence.

In eukaryotes, ORFs in exons are often interrupted by introns.

Start and stop codons

Translation starts with a chain-initiation codon or start codon. The start codon alone is not sufficient to begin the process. Nearby sequences such as the Shine-Dalgarno sequence in E. coli and initiation factors are also required to start translation. The most common start codon is AUG, which is read as methionine or, in bacteria, as formylmethionine. Alternative start codons depending on the organism include "GUG" or "UUG"; these codons normally represent valine and leucine, respectively, but as start codons they are translated as methionine or formylmethionine. [24]

The three stop codons have names: UAG is amber, UGA is opal (sometimes also called umber), and UAA is ochre. Stop codons are also called "termination" or "nonsense" codons. They signal release of the nascent polypeptide from the ribosome because no cognate tRNA has anticodons complementary to these stop signals, allowing a release factor to bind to the ribosome instead. [25]

Effect of mutations

Examples of notable mutations that can occur in humans. Notable mutations.svg
Examples of notable mutations that can occur in humans.

During the process of DNA replication, errors occasionally occur in the polymerization of the second strand. These errors, mutations, can affect an organism's phenotype, especially if they occur within the protein coding sequence of a gene. Error rates are typically 1 error in every 10–100 million bases—due to the "proofreading" ability of DNA polymerases. [27] [28]

Missense mutations and nonsense mutations are examples of point mutations that can cause genetic diseases such as sickle-cell disease and thalassemia respectively. [29] [30] [31] Clinically important missense mutations generally change the properties of the coded amino acid residue among basic, acidic, polar or non-polar states, whereas nonsense mutations result in a stop codon. [23]

Mutations that disrupt the reading frame sequence by indels (insertions or deletions) of a non-multiple of 3 nucleotide bases are known as frameshift mutations. 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. [32] These mutations may impair the protein's function and are thus rare in in vivo protein-coding sequences. One reason inheritance of frameshift mutations is rare is that, if the protein being translated is essential for growth under the selective pressures the organism faces, absence of a functional protein may cause death before the organism becomes viable. [33] Frameshift mutations may result in severe genetic diseases such as Tay–Sachs disease. [34]

Although most mutations that change protein sequences are harmful or neutral, some mutations have benefits. [35] These mutations may enable the mutant organism to withstand particular environmental stresses better than wild type organisms, or reproduce more quickly. In these cases a mutation will tend to become more common in a population through natural selection. [36] Viruses that use RNA as their genetic material have rapid mutation rates, [37] which can be an advantage, since these viruses thereby evolve rapidly, and thus evade the immune system defensive responses. [38] In large populations of asexually reproducing organisms, for example, E. coli, multiple beneficial mutations may co-occur. This phenomenon is called clonal interference and causes competition among the mutations. [39]


Grouping of codons by amino acid residue molar volume and hydropathicity. A more detailed version is available. Genetic Code Simple Corrected.pdf
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. 3D Genetic Code.jpg
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.

Degeneracy is the redundancy of the genetic code. This term was given by Bernfield and Nirenberg. The genetic code has redundancy but no ambiguity (see the codon tables below for the full correlation). For example, although codons GAA and GAG both specify glutamic acid (redundancy), neither specifies another amino acid (no ambiguity). The codons encoding one amino acid may differ in any of their three positions. 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). [40] 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. NCN yields amino acid residues that are small in size and moderate in hydropathicity; NAN encodes average size hydrophilic residues. 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. [41] [42] Note in the table, below, eight amino acids are not affected at all by mutations at the third position of the codon, whereas in the figure above, a mutation at the second position is likely to cause a radical change in the physicochemical properties of the encoded amino acid. Nevertheless, changes in the first position of the codons are more important than changes in the second position on a global scale. [43] The reason may be that charge reversal (from a positive to a negative charge or vice versa) can only occur upon mutations in the first position of certain codons, but not upon changes in the second position of any codon. Such charge reversal may have dramatic consequences for the structure or function of a protein. This aspect may have been largely underestimated by previous studies. [43]

Codon usage bias

The frequency of codons, also known as codon usage bias, can vary from species to species with functional implications for the control of translation.

Human genome codon frequency table
Human genome codon frequency [44]
CodonAA [C] Fraction [D] Freq [E] Number [F] CodonAAFractionFreq NumberCodonAAFractionFreq NumberCodonAAFractionFreq Number

Alternative genetic codes

Non-standard amino acids

In some proteins, non-standard amino acids are substituted for standard stop codons, depending on associated signal sequences in the messenger RNA. For example, UGA can code for selenocysteine and UAG can code for pyrrolysine. Selenocysteine came to be seen as the 21st amino acid, and pyrrolysine as the 22nd. [45] Unlike selenocysteine, pyrrolysine-encoded UAG is translated with the participation of a dedicated aminoacyl-tRNA synthetase. [46] Both selenocysteine and pyrrolysine may be present in the same organism. [45] Although the genetic code is normally fixed in an organism, the achaeal prokaryote Acetohalobium arabaticum can expand its genetic code from 20 to 21 amino acids (by including pyrrolysine) under different conditions of growth. [47]


Genetic code logo of the Globobulimina pseudospinescens mitochondrial genome. 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. FACIL genetic code logo.png
Genetic code logo of the Globobulimina pseudospinescens mitochondrial genome. 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.

Variations on the standard code were predicted in the 1970s. [48] The first was discovered in 1979, by researchers studying human mitochondrial genes. [49] Many slight variants were discovered thereafter, [50] including various alternative mitochondrial codes. [51] These minor variants for example involve translation of the codon UGA as tryptophan in Mycoplasma species, and translation of CUG as a serine rather than leucine in yeasts of the "CTG clade" (such as Candida albicans ). [52] [53] [54] Because viruses must use the same genetic code as their hosts, modifications to the standard genetic code could interfere with viral protein synthesis or functioning. However, viruses such as totiviruses have adapted to the host's genetic code modification. [55] In bacteria and archaea, GUG and UUG are common start codons. In rare cases, certain proteins may use alternative start codons. [50] 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. [56] This type of recoding is induced by a high-readthrough stop codon context [57] and it is referred to as functional translational readthrough. [58]

Variant genetic codes used by an organism can be inferred by identifying highly conserved genes encoded in that genome, and comparing its codon usage to the amino acids in homologous proteins of other organisms. For example, the program FACIL [59] infers a genetic code by searching which amino acids in homologous protein domains are most often aligned to every codon. The resulting amino acid probabilities for each codon are displayed in a genetic code logo, that also shows the support for a stop codon.

Despite these differences, all known naturally occurring codes are very similar. The coding mechanism is the same for all organisms: three-base codons, tRNA, ribosomes, single direction reading and translating single codons into single amino acids. [60] 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 [61] or trigger ribosomal frameshifting as in Euplotes . [62]


The genetic code is a key part of the history of life, according to one version of which self-replicating RNA molecules preceded life as we know it. This is the RNA world hypothesis. Under this hypothesis, any model for the emergence of the genetic code is intimately related to a model of the transfer from ribozymes (RNA enzymes) to proteins as the principal enzymes in cells. In line with the RNA world hypothesis, transfer RNA molecules appear to have evolved before modern aminoacyl-tRNA synthetases, so the latter cannot be part of the explanation of its patterns. [63]

A hypothetical randomly evolved genetic code further motivates a biochemical or evolutionary model for its origin. If amino acids were randomly assigned to triplet codons, there would be 1.5 × 1084 possible genetic codes. [64] : 163 This number is found by calculating the number of ways that 21 items (20 amino acids plus one stop) can be placed in 64 bins, wherein each item is used at least once. [65] However, the distribution of codon assignments in the genetic code is nonrandom. [66] In particular, the genetic code clusters certain amino acid assignments.

Amino acids that share the same biosynthetic pathway tend to have the same first base in their codons. This could be an evolutionary relic of an early, simpler genetic code with fewer amino acids that later evolved to code a larger set of amino acids. [67] It could also reflect steric and chemical properties that had another effect on the codon during its evolution. Amino acids with similar physical properties also tend to have similar codons, [68] [69] reducing the problems caused by point mutations and mistranslations. [66]

Given the non-random genetic triplet coding scheme, a tenable hypothesis for the origin of genetic code could address multiple aspects of the codon table, such as absence of codons for D-amino acids, secondary codon patterns for some amino acids, confinement of synonymous positions to third position, the small set of only 20 amino acids (instead of a number approaching 64), and the relation of stop codon patterns to amino acid coding patterns. [70]

Three main hypotheses address the origin of the genetic code. Many models belong to one of them or to a hybrid: [71]

Hypotheses have addressed a variety of scenarios: [75]

See also

Related Research Articles

Mutation Alteration in the nucleotide sequence of a genome

In biology, a mutation is an alteration in the nucleotide sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA, which then may undergo error-prone repair, cause an error during other forms of repair, or cause an error during replication. Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements.

Stop codon Codon that marks the end of a protein-coding sequence

In molecular biology, a stop codon is a codon that signals the termination of the translation process of the current protein. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide chain, which may ultimately become a protein; stop codons signal the termination of this process by binding release factors, which cause the ribosomal subunits to disassociate, releasing the amino acid chain.

Pyrrolysine Chemical compound

Pyrrolysine is an α-amino acid that is used in the biosynthesis of proteins in some methanogenic archaea and bacteria; it is not present in humans. It contains an α-amino group, a carboxylic acid group. Its pyrroline side-chain is similar to that of lysine in being basic and positively charged at neutral pH.

Central dogma of molecular biology Explanation of the flow of genetic information within a biological system

The central dogma of molecular biology is an explanation of the flow of genetic information within a biological system. It is often stated as "DNA makes RNA, and RNA makes protein", although this is not its original meaning. It was first stated by Francis Crick in 1957, then published in 1958:

The Central Dogma. This states that once "information" has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein.

Codon usage bias A genetic bias towards the preferential use of one of the redundant codons that encode the same amino acid over the others

Codon usage bias refers to differences in the frequency of occurrence of synonymous codons in coding DNA. A codon is a series of three nucleotides that encodes a specific amino acid residue in a polypeptide chain or for the termination of translation.

Translation (biology) Cellular process of protein synthesis

In molecular biology and genetics, translation is the process in which ribosomes in the cytoplasm or endoplasmic reticulum synthesize proteins after the process of transcription of DNA to RNA in the cell's nucleus. The entire process is called gene expression.

Proteinogenic amino acid Amino acid that is incorporated biosynthetically into proteins during translation

Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) amino acids, 20 in the standard genetic code and an additional 2 that can be incorporated by special translation mechanisms.

Reading frame

In molecular biology, a reading frame is a way of dividing the sequence of nucleotides in a nucleic acid molecule into a set of consecutive, non-overlapping triplets. Where these triplets equate to amino acids or stop signals during translation, they are called codons.

Transfer RNA RNA that facilitates the addition of amino acids to a new protein

A transfer RNA is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length, that serves as the physical link between the mRNA and the amino acid sequence of proteins. Transfer RNA (tRNA) does this by carrying an amino acid to the protein synthetic machinery of a cell called the ribosome. Complementation of a 3-nucleotide codon in a messenger RNA (mRNA) by a 3-nucleotide anticodon of the tRNA results in protein synthesis based on the mRNA code. As such, tRNAs are a necessary component of translation, the biological synthesis of new proteins in accordance with the genetic code.

Frameshift mutation Mutation that shifts codon alignment

A frameshift mutation is a genetic mutation caused by indels of a number of nucleotides in a DNA sequence that is not divisible by three. Due to the triplet nature of gene expression by codons, the insertion or deletion can change the reading frame, resulting in a completely different translation from the original. The earlier in the sequence the deletion or insertion occurs, the more altered the protein. A frameshift mutation is not the same as a single-nucleotide polymorphism in which a nucleotide is replaced, rather than inserted or deleted. A frameshift mutation will in general cause the reading of the codons after the mutation to code for different amino acids. The frameshift mutation will also alter the first stop codon encountered in the sequence. The polypeptide being created could be abnormally short or abnormally long, and will most likely not be functional.

Point mutation Replacement, insertion, or deletion of a single DNA or RNA nucleotide

A point mutation or substitution is a genetic mutation where a single nucleotide base is changed, inserted or deleted from a DNA or RNA sequence of an organism's genome. Point mutations have a variety of effects on the downstream protein product—consequences that are moderately predictable based upon the specifics of the mutation. These consequences can range from no effect to deleterious effects, with regard to protein production, composition, and function.

The Nirenberg and Matthaei experiment was a scientific experiment performed in May 1961 by Marshall W. Nirenberg and his post-doctoral fellow, J. Heinrich Matthaei at the National Institutes of Health (NIH). The experiment deciphered the first of the 64 triplet codons in the genetic code by using nucleic acid homopolymers to translate specific amino acids.

Nirenberg and Leder experiment

The Nirenberg and Leder experiment was a scientific experiment performed in 1964 by Marshall W. Nirenberg and Philip Leder. The experiment elucidated the triplet nature of the genetic code and allowed the remaining ambiguous codons in the genetic code to be deciphered.

A synonymous substitution is the evolutionary substitution of one base for another in an exon of a gene coding for a protein, such that the produced amino acid sequence is not modified. This is possible because the genetic code is "degenerate", meaning that some amino acids are coded for by more than one three-base-pair codon; since some of the codons for a given amino acid differ by just one base pair from others coding for the same amino acid, a mutation that replaces the "normal" base by one of the alternatives will result in incorporation of the same amino acid into the growing polypeptide chain when the gene is translated. Synonymous substitutions and mutations affecting noncoding DNA are often considered silent mutations; however, it is not always the case that the mutation is silent.

Start codon First codon of a messenger RNA transcript translated by a ribosome

The start codon is the first codon of a messenger RNA (mRNA) transcript translated by a ribosome. The start codon always codes for methionine in eukaryotes and Archaea and a N-formylmethionine (fMet) in bacteria, mitochondria and plastids. The most common start codon is AUG.

Gene Sequence of DNA or RNA that codes for an RNA or protein product

In biology, a gene is a basic unit of heredity and a sequence of nucleotides in DNA or RNA that encodes the synthesis of a gene product, either RNA or protein.

Neutral mutations are changes in DNA sequence that are neither beneficial nor detrimental to the ability of an organism to survive and reproduce. In population genetics, mutations in which natural selection does not affect the spread of the mutation in a species are termed neutral mutations. Neutral mutations that are inheritable and not linked to any genes under selection will either be lost or will replace all other alleles of the gene. This loss or fixation of the gene proceeds based on random sampling known as genetic drift. A neutral mutation that is in linkage disequilibrium with other alleles that are under selection may proceed to loss or fixation via genetic hitchhiking and/or background selection.

Expanded genetic code

An expanded genetic code is an artificially modified genetic code in which one or more specific codons have been re-allocated to encode an amino acid that is not among the 22 common naturally-encoded proteinogenic amino acids.

DNA and RNA codon tables List of standard rules to translate DNA encoded information into proteins

A codon table can be used to translate a genetic code into a sequence of amino acids. The standard genetic code is traditionally represented as an RNA codon table, because when proteins are made in a cell by ribosomes, it is messenger RNA that directs protein biosynthesis. The mRNA sequence is determined by the sequence of genomic DNA. In such context, the standard genetic code is referred to as translation table 1. It can also be represented in a DNA codon table. The DNA codons in such tables occur on the sense DNA strand and are arranged in a 5′-to-3′ direction. Different tables with alternate codons are used depending on the source of the genetic code, such as from a cell nucleus, mitochondrion, plastid, or hydrogenosome.

Transcription-translation coupling is a mechanism of gene expression regulation in which synthesis of an mRNA (transcription) is affected by its concurrent decoding (translation). In prokaryotes, mRNAs are translated while they are transcribed. This allows communication between RNA polymerase, the multisubunit enzyme that catalyzes transcription, and the ribosome, which catalyzes translation. Coupling involves both direct physical interactions between RNA polymerase and the ribosome, as well as ribosome-induced changes to the structure and accessibility of the intervening mRNA that affect transcription.


  1. Turanov AA, Lobanov AV, Fomenko DE, Morrison HG, Sogin ML, Klobutcher LA, Hatfield DL, Gladyshev VN (January 2009). "Genetic code supports targeted insertion of two amino acids by one codon". Science. 323 (5911): 259–61. doi:10.1126/science.1164748. PMC   3088105 . PMID   19131629.
  2. Crick, Francis (10 July 1990). "Chapter 8: The genetic code". What Mad Pursuit: A Personal View of Scientific Discovery. Basic Books. pp. 89–101. ISBN   978-0-465-09138-6.
  3. Yanofsky, Charles (9 March 2007). "Establishing the Triplet Nature of the Genetic Code". Cell. 128 (5): 815–818. doi: 10.1016/j.cell.2007.02.029 . PMID   17350564. S2CID   14249277.
  4. Nirenberg MW, Matthaei JH (October 1961). "The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides". Proceedings of the National Academy of Sciences of the United States of America. 47 (10): 1588–602. Bibcode:1961PNAS...47.1588N. doi: 10.1073/pnas.47.10.1588 . PMC   223178 . PMID   14479932.
  5. Gardner RS, Wahba AJ, Basilio C, Miller RS, Lengyel P, Speyer JF (December 1962). "Synthetic polynucleotides and the amino acid code. VII". Proceedings of the National Academy of Sciences of the United States of America. 48 (12): 2087–94. Bibcode:1962PNAS...48.2087G. doi: 10.1073/pnas.48.12.2087 . PMC   221128 . PMID   13946552.
  6. Wahba AJ, Gardner RS, Basilio C, Miller RS, Speyer JF, Lengyel P (January 1963). "Synthetic polynucleotides and the amino acid code. VIII". Proceedings of the National Academy of Sciences of the United States of America. 49 (1): 116–22. Bibcode:1963PNAS...49..116W. doi: 10.1073/pnas.49.1.116 . PMC   300638 . PMID   13998282.
  7. "The Nobel Prize in Physiology or Medicine 1959" (Press release). The Royal Swedish Academy of Science. 1959. Retrieved 27 February 2010. The Nobel Prize in Physiology or Medicine 1959 was awarded jointly to Severo Ochoa and Arthur Kornberg 'for their discovery of the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid'.
  8. Nirenberg M, Leder P, Bernfield M, Brimacombe R, Trupin J, Rottman F, O'Neal C (May 1965). "RNA codewords and protein synthesis, VII. On the general nature of the RNA code". Proceedings of the National Academy of Sciences of the United States of America. 53 (5): 1161–8. Bibcode:1965PNAS...53.1161N. doi: 10.1073/pnas.53.5.1161 . PMC   301388 . PMID   5330357.
  9. "The Nobel Prize in Physiology or Medicine 1968" (Press release). The Royal Swedish Academy of Science. 1968. Retrieved 27 February 2010. The Nobel Prize in Physiology or Medicine 1968 was awarded jointly to Robert W. Holley, Har Gobind Khorana and Marshall W. Nirenberg 'for their interpretation of the genetic code and its function in protein synthesis'.
  10. Edgar B (October 2004). "The genome of bacteriophage T4: an archeological dig". Genetics. 168 (2): 575–82. doi:10.1093/genetics/168.2.575. PMC   1448817 . PMID   15514035.
  11. Budisa, Nediljko (23 December 2005). The book at the Wiley Online Library. doi:10.1002/3527607188. ISBN   9783527312436.
  12. Kubyshkin, V.; Budisa, N. (2017). "Synthetic alienation of microbial organisms by using genetic code engineering: Why and how?". Biotechnology Journal. 12 (8): 1600097. doi:10.1002/biot.201600097. PMID   28671771.
  13. Xie J, Schultz PG (December 2005). "Adding amino acids to the genetic repertoire". Current Opinion in Chemical Biology. 9 (6): 548–54. doi:10.1016/j.cbpa.2005.10.011. PMID   16260173.
  14. Wang Q, Parrish AR, Wang L (March 2009). "Expanding the genetic code for biological studies". Chemistry & Biology. 16 (3): 323–36. doi:10.1016/j.chembiol.2009.03.001. PMC   2696486 . PMID   19318213.
  15. Simon M (7 January 2005). Emergent Computation: Emphasizing Bioinformatics. Springer Science & Business Media. pp. 105–106. ISBN   978-0-387-22046-8.
  16. Hoesl, M. G.; Oehm, S.; Durkin, P.; Darmon, E.; Peil, L.; Aerni, H.-R.; Rappsilber, J.; Rinehart, J.; Leach, D.; Söll, D.; Budisa, N. (2015). "Chemical evolution of a bacterial proteome". Angewandte Chemie International Edition. 54 (34): 10030–10034. doi:10.1002/anie.201502868. PMC   4782924 . PMID   26136259. NIHMSID: NIHMS711205
  17. "First stable semisynthetic organism created | KurzweilAI". 3 February 2017. Retrieved 9 February 2017.
  18. Zhang Y, Lamb BM, Feldman AW, Zhou AX, Lavergne T, Li L, Romesberg FE (February 2017). "A semisynthetic organism engineered for the stable expansion of the genetic alphabet". Proceedings of the National Academy of Sciences of the United States of America. 114 (6): 1317–1322. doi: 10.1073/pnas.1616443114 . PMC   5307467 . PMID   28115716.
  19. Han S, Yang A, Lee S, Lee HW, Park CB, Park HS (February 2017). "Expanding the genetic code of Mus musculus". Nature Communications. 8: 14568. Bibcode:2017NatCo...814568H. doi:10.1038/ncomms14568. PMC   5321798 . PMID   28220771.
  20. Zimmer, Carl (15 May 2019). "Scientists Created Bacteria With a Synthetic Genome. Is This Artificial Life? - In a milestone for synthetic biology, colonies of E. coli thrive with DNA constructed from scratch by humans, not nature". The New York Times . Retrieved 16 May 2019.
  21. Fredens, Julius; et al. (15 May 2019). "Total synthesis of Escherichia coli with a recoded genome". Nature . 569 (7757): 514–518. Bibcode:2019Natur.569..514F. doi:10.1038/s41586-019-1192-5. PMC   7039709 . PMID   31092918. S2CID   205571025.
  22. Homo sapiens mitochondrion, complete genome. "Revised Cambridge Reference Sequence (rCRS): accession NC_012920", National Center for Biotechnology Information . Retrieved on 27 December 2017.
  23. 1 2 King RC, Mulligan P, Stansfield W (10 January 2013). A Dictionary of Genetics. OUP USA. p. 608. ISBN   978-0-19-976644-4.
  24. Touriol C, Bornes S, Bonnal S, Audigier S, Prats H, Prats AC, Vagner S (2003). "Generation of protein isoform diversity by alternative initiation of translation at non-AUG codons". Biology of the Cell. 95 (3–4): 169–78. doi: 10.1016/S0248-4900(03)00033-9 . PMID   12867081.
  25. Maloy S (29 November 2003). "How nonsense mutations got their names". Microbial Genetics Course. San Diego State University. Retrieved 10 March 2010.
  26. References for the image are found in Wikimedia Commons page at: Commons:File:Notable mutations.svg#References.
  27. Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, et al., eds. (2000). "Spontaneous mutations". An Introduction to Genetic Analysis (7th ed.). New York: W. H. Freeman. ISBN   978-0-7167-3520-5.
  28. Freisinger E, Grollman AP, Miller H, Kisker C (April 2004). "Lesion (in)tolerance reveals insights into DNA replication fidelity". The EMBO Journal. 23 (7): 1494–505. doi:10.1038/sj.emboj.7600158. PMC   391067 . PMID   15057282.
  29. ( Boillée 2006 , p. 39)
  30. Chang JC, Kan YW (June 1979). "beta 0 thalassemia, a nonsense mutation in man". Proceedings of the National Academy of Sciences of the United States of America. 76 (6): 2886–9. Bibcode:1979PNAS...76.2886C. doi: 10.1073/pnas.76.6.2886 . PMC   383714 . PMID   88735.
  31. Boillée S, Vande Velde C, Cleveland DW (October 2006). "ALS: a disease of motor neurons and their nonneuronal neighbors". Neuron. 52 (1): 39–59. doi: 10.1016/j.neuron.2006.09.018 . PMID   17015226.
  32. Isbrandt D, Hopwood JJ, von Figura K, Peters C (1996). "Two novel frameshift mutations causing premature stop codons in a patient with the severe form of Maroteaux-Lamy syndrome". Human Mutation. 7 (4): 361–3. doi:10.1002/(SICI)1098-1004(1996)7:4<361::AID-HUMU12>3.0.CO;2-0. PMID   8723688.
  33. Crow JF (1993). "How much do we know about spontaneous human mutation rates?". Environmental and Molecular Mutagenesis. 21 (2): 122–9. doi:10.1002/em.2850210205. PMID   8444142. S2CID   32918971.
  34. Lewis R (2005). Human Genetics: Concepts and Applications (6th ed.). Boston, Mass: McGraw Hill. pp. 227–228. ISBN   978-0-07-111156-0.
  35. Sawyer SA, Parsch J, Zhang Z, Hartl DL (April 2007). "Prevalence of positive selection among nearly neutral amino acid replacements in Drosophila". Proceedings of the National Academy of Sciences of the United States of America. 104 (16): 6504–10. Bibcode:2007PNAS..104.6504S. doi: 10.1073/pnas.0701572104 . PMC   1871816 . PMID   17409186.
  36. Bridges KR (2002). "Malaria and the Red Cell". Harvard. Archived from the original on 27 November 2011.
  37. Drake JW, Holland JJ (November 1999). "Mutation rates among RNA viruses". Proceedings of the National Academy of Sciences of the United States of America. 96 (24): 13910–3. Bibcode:1999PNAS...9613910D. doi: 10.1073/pnas.96.24.13910 . PMC   24164 . PMID   10570172.
  38. Holland J, Spindler K, Horodyski F, Grabau E, Nichol S, VandePol S (March 1982). "Rapid evolution of RNA genomes". Science. 215 (4540): 1577–85. Bibcode:1982Sci...215.1577H. doi:10.1126/science.7041255. PMID   7041255.
  39. de Visser JA, Rozen DE (April 2006). "Clonal interference and the periodic selection of new beneficial mutations in Escherichia coli". Genetics. 172 (4): 2093–100. doi:10.1534/genetics.105.052373. PMC   1456385 . PMID   16489229.
  40. Watson, James D. (2008). Molecular Biology of the Gene. Pearson/Benjamin Cummings. ISBN   978-0-8053-9592-1.: 102–117 : 521–522
  41. Michel-Beyerle, Maria Elisabeth (1990). Reaction centers of photosynthetic bacteria: Feldafing-II-Meeting. Springer-Verlag. ISBN   978-3-540-53420-4.
  42. Füllen G, Youvan DC (1994). "Genetic Algorithms and Recursive Ensemble Mutagenesis in Protein Engineering". Complexity International 1.
  43. 1 2 Fricke, Markus (2019). "Global importance of RNA secondary structures in protein coding sequences". Bioinformatics. 35 (4): 579–583. doi:10.1093/bioinformatics/bty678. PMC   7109657 . PMID   30101307. S2CID   51968530.
  44. "Codon usage table".
  45. 1 2 Zhang Y, Baranov PV, Atkins JF, Gladyshev VN (May 2005). "Pyrrolysine and selenocysteine use dissimilar decoding strategies". The Journal of Biological Chemistry. 280 (21): 20740–51. doi: 10.1074/jbc.M501458200 . PMID   15788401.
  46. Krzycki JA (December 2005). "The direct genetic encoding of pyrrolysine". Current Opinion in Microbiology. 8 (6): 706–12. doi:10.1016/j.mib.2005.10.009. PMID   16256420.
  47. Prat L, Heinemann IU, Aerni HR, Rinehart J, O'Donoghue P, Söll D (December 2012). "Carbon source-dependent expansion of the genetic code in bacteria". Proceedings of the National Academy of Sciences of the United States of America. 109 (51): 21070–5. Bibcode:2012PNAS..10921070P. doi: 10.1073/pnas.1218613110 . PMC   3529041 . PMID   23185002.
  48. Crick FH, Orgel LE (1973). "Directed panspermia". Icarus. 19 (3): 341–6, 344. Bibcode:1973Icar...19..341C. doi:10.1016/0019-1035(73)90110-3. It is a little surprising that organisms with somewhat different codes do not coexist. (Further discussion)
  49. Barrell BG, Bankier AT, Drouin J (1979). "A different genetic code in human mitochondria". Nature. 282 (5735): 189–194. Bibcode:1979Natur.282..189B. doi:10.1038/282189a0. PMID   226894. S2CID   4335828. ()
  50. 1 2 Elzanowski A, Ostell J (7 April 2008). "The Genetic Codes". National Center for Biotechnology Information (NCBI). Retrieved 10 March 2010.
  51. Jukes TH, Osawa S (December 1990). "The genetic code in mitochondria and chloroplasts". Experientia. 46 (11–12): 1117–26. doi:10.1007/BF01936921. PMID   2253709. S2CID   19264964.
  52. Fitzpatrick DA, Logue ME, Stajich JE, Butler G (1 January 2006). "A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis". BMC Evolutionary Biology. 6: 99. doi:10.1186/1471-2148-6-99. PMC   1679813 . PMID   17121679.
  53. Santos MA, Tuite MF (May 1995). "The CUG codon is decoded in vivo as serine and not leucine in Candida albicans". Nucleic Acids Research. 23 (9): 1481–6. doi:10.1093/nar/23.9.1481. PMC   306886 . PMID   7784200.
  54. Butler G, Rasmussen MD, Lin MF, et al. (June 2009). "Evolution of pathogenicity and sexual reproduction in eight Candida genomes". Nature. 459 (7247): 657–62. Bibcode:2009Natur.459..657B. doi:10.1038/nature08064. PMC   2834264 . PMID   19465905.
  55. Taylor DJ, Ballinger MJ, Bowman SM, Bruenn JA (2013). "Virus-host co-evolution under a modified nuclear genetic code". PeerJ. 1: e50. doi:10.7717/peerj.50. PMC   3628385 . PMID   23638388.
  56. Hofhuis J, Schueren F, Nötzel C, Lingner T, Gärtner J, Jahn O, Thoms S (2016). "The functional readthrough extension of malate dehydrogenase reveals a modification of the genetic code". Open Biol. 6 (11): 160246. doi:10.1098/rsob.160246. PMC   5133446 . PMID   27881739.
  57. Schueren F, Lingner T, George R, Hofhuis J, Gartner J, Thoms S (2014). "Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals". eLife. 3: e03640. doi:10.7554/eLife.03640. PMC   4359377 . PMID   25247702.
  58. F. Schueren und S. Thoms (2016). "Functional Translational Readthrough: A Systems Biology Perspective". PLOS Genetics. 12 (8): e1006196. doi:10.1371/journal.pgen.1006196. PMC   4973966 . PMID   27490485.
  59. Dutilh BE, Jurgelenaite R, Szklarczyk R, van Hijum SA, Harhangi HR, Schmid M, de Wild B, Françoijs KJ, Stunnenberg HG, Strous M, Jetten MS, Op den Camp HJ, Huynen MA (July 2011). "FACIL: Fast and Accurate Genetic Code Inference and Logo". Bioinformatics. 27 (14): 1929–33. doi:10.1093/bioinformatics/btr316. PMC   3129529 . PMID   21653513.
  60. Kubyshkin V, Acevedo-Rocha CG, Budisa N (February 2018). "On universal coding events in protein biogenesis". Bio Systems. 164: 16–25. doi: 10.1016/j.biosystems.2017.10.004 . PMID   29030023.
  61. Heaphy SM, Mariotti M, Gladyshev VN, Atkins JF, Baranov PV (November 2016). "Novel Ciliate Genetic Code Variants Including the Reassignment of All Three Stop Codons to Sense Codons in Condylostoma magnum". Molecular Biology and Evolution. 33 (11): 2885–2889. doi:10.1093/molbev/msw166. PMC   5062323 . PMID   27501944.
  62. Lobanov AV, Heaphy SM, Turanov AA, Gerashchenko MV, Pucciarelli S, Devaraj RR, et al. (January 2017). "Position-dependent termination and widespread obligatory frameshifting in Euplotes translation". Nature Structural & Molecular Biology. 24 (1): 61–68. doi:10.1038/nsmb.3330. PMC   5295771 . PMID   27870834.
  63. Ribas de Pouplana L, Turner RJ, Steer BA, Schimmel P (September 1998). "Genetic code origins: tRNAs older than their synthetases?". Proceedings of the National Academy of Sciences of the United States of America. 95 (19): 11295–300. Bibcode:1998PNAS...9511295D. doi: 10.1073/pnas.95.19.11295 . PMC   21636 . PMID   9736730.
  64. 1 2 Yarus, Michael (2010). Life from an RNA World: The Ancestor Within. Harvard University Press. ISBN   978-0-674-05075-4.
  65. "Mathematica function for # possible arrangements of items in bins? – Online Technical Discussion Groups—Wolfram Community". Retrieved 3 February 2017.
  66. 1 2 Freeland SJ, Hurst LD (September 1998). "The genetic code is one in a million". Journal of Molecular Evolution. 47 (3): 238–48. Bibcode:1998JMolE..47..238F. doi:10.1007/PL00006381. PMID   9732450. S2CID   20130470.
  67. Taylor FJ, Coates D (1989). "The code within the codons". Bio Systems. 22 (3): 177–87. doi:10.1016/0303-2647(89)90059-2. PMID   2650752.
  68. Di Giulio M (October 1989). "The extension reached by the minimization of the polarity distances during the evolution of the genetic code". Journal of Molecular Evolution. 29 (4): 288–93. Bibcode:1989JMolE..29..288D. doi:10.1007/BF02103616. PMID   2514270. S2CID   20803686.
  69. Wong JT (February 1980). "Role of minimization of chemical distances between amino acids in the evolution of the genetic code". Proceedings of the National Academy of Sciences of the United States of America. 77 (2): 1083–6. Bibcode:1980PNAS...77.1083W. doi: 10.1073/pnas.77.2.1083 . PMC   348428 . PMID   6928661.
  70. 1 2 3 4 Erives A (August 2011). "A model of proto-anti-codon RNA enzymes requiring L-amino acid homochirality". Journal of Molecular Evolution. 73 (1–2): 10–22. Bibcode:2011JMolE..73...10E. doi:10.1007/s00239-011-9453-4. PMC   3223571 . PMID   21779963.
  71. 1 2 Freeland SJ, Knight RD, Landweber LF, Hurst LD (April 2000). "Early fixation of an optimal genetic code". Molecular Biology and Evolution. 17 (4): 511–18. doi: 10.1093/oxfordjournals.molbev.a026331 . PMID   10742043.
  72. Crick FH (December 1968). "The origin of the genetic code". Journal of Molecular Evolution. 38 (3): 367–79. doi:10.1016/0022-2836(68)90392-6. PMID   4887876.
  73. Hopfield JJ (1978). "Origin of the genetic code: a testable hypothesis based on tRNA structure, sequence, and kinetic proofreading". PNAS. 75 (9): 4334–4338. Bibcode:1978PNAS...75.4334H. doi: 10.1073/pnas.75.9.4334 . PMC   336109 . PMID   279919.
  74. 1 2 Yarus M, Widmann JJ, Knight R (November 2009). "RNA-amino acid binding: a stereochemical era for the genetic code". Journal of Molecular Evolution. 69 (5): 406–29. Bibcode:2009JMolE..69..406Y. doi: 10.1007/s00239-009-9270-1 . PMID   19795157.
  75. Knight RD, Freeland SJ, Landweber LF (June 1999). "Selection, history and chemistry: the three faces of the genetic code" (PDF). Trends in Biochemical Sciences. 24 (6): 241–7. doi:10.1016/S0968-0004(99)01392-4. PMID   10366854.
  76. Knight RD, Landweber LF (September 1998). "Rhyme or reason: RNA-arginine interactions and the genetic code". Chemistry & Biology. 5 (9): R215–20. doi: 10.1016/S1074-5521(98)90001-1 . PMID   9751648.
  77. Sengupta S, Higgs PG (2015). "Pathways of genetic code evolution in ancient and modern organisms". Journal of Molecular Evolution. 80 (5–6): 229–243. Bibcode:2015JMolE..80..229S. doi:10.1007/s00239-015-9686-8. PMID   26054480. S2CID   15542587.
  78. Brooks DJ, Fresco JR, Lesk AM, Singh M (October 2002). "Evolution of amino acid frequencies in proteins over deep time: inferred order of introduction of amino acids into the genetic code". Molecular Biology and Evolution. 19 (10): 1645–55. doi: 10.1093/oxfordjournals.molbev.a003988 . PMID   12270892.
  79. Amirnovin R (May 1997). "An analysis of the metabolic theory of the origin of the genetic code". Journal of Molecular Evolution. 44 (5): 473–6. Bibcode:1997JMolE..44..473A. doi:10.1007/PL00006170. PMID   9115171. S2CID   23334860.
  80. Ronneberg TA, Landweber LF, Freeland SJ (December 2000). "Testing a biosynthetic theory of the genetic code: fact or artifact?". Proceedings of the National Academy of Sciences of the United States of America. 97 (25): 13690–5. Bibcode:2000PNAS...9713690R. doi: 10.1073/pnas.250403097 . PMC   17637 . PMID   11087835.
  81. Trifonov, Edward N. (September 2009). "The origin of the genetic code and of the earliest oligopeptides". Research in Microbiology. 160 (7): 481–486. doi:10.1016/j.resmic.2009.05.004. PMID   19524038.
  82. Higgs, Paul G.; Pudritz, Ralph E. (June 2009). "A Thermodynamic Basis for Prebiotic Amino Acid Synthesis and the Nature of the First Genetic Code". Astrobiology. 9 (5): 483–490. arXiv: 0904.0402 . Bibcode:2009AsBio...9..483H. doi:10.1089/ast.2008.0280. ISSN   1531-1074. PMID   19566427. S2CID   9039622.
  83. Chaliotis, Anargyros; Vlastaridis, Panayotis; Mossialos, Dimitris; Ibba, Michael; Becker, Hubert D.; Stathopoulos, Constantinos; Amoutzias, Grigorios D. (17 February 2017). "The complex evolutionary history of aminoacyl-tRNA synthetases". Nucleic Acids Research. 45 (3): 1059–1068. doi:10.1093/nar/gkw1182. ISSN   0305-1048. PMC   5388404 . PMID   28180287.
  84. Ntountoumi, Chrysa; Vlastaridis, Panayotis; Mossialos, Dimitris; Stathopoulos, Constantinos; Iliopoulos, Ioannis; Promponas, Vasilios; Oliver, Stephen G; Amoutzias, Grigoris D (4 November 2019). "Low complexity regions in the proteins of prokaryotes perform important functional roles and are highly conserved". Nucleic Acids Research. 47 (19): 9998–10009. doi:10.1093/nar/gkz730. ISSN   0305-1048. PMC   6821194 . PMID   31504783.
  85. 1 2 Freeland SJ, Wu T, Keulmann N (October 2003). "The case for an error minimizing standard genetic code". Origins of Life and Evolution of the Biosphere. 33 (4–5): 457–77. Bibcode:2003OLEB...33..457F. doi:10.1023/A:1025771327614. PMID   14604186. S2CID   18823745.
  86. Baranov PV, Venin M, Provan G (2009). Gemmell NJ (ed.). "Codon size reduction as the origin of the triplet genetic code". PLOS ONE. 4 (5): e5708. Bibcode:2009PLoSO...4.5708B. doi: 10.1371/journal.pone.0005708 . PMC   2682656 . PMID   19479032.
  87. Tlusty T (November 2007). "A model for the emergence of the genetic code as a transition in a noisy information channel". Journal of Theoretical Biology. 249 (2): 331–42. arXiv: 1007.4122 . doi:10.1016/j.jtbi.2007.07.029. PMID   17826800. S2CID   12206140.
  88. Sonneborn TM (1965). Bryson V, Vogel H (eds.). Evolving genes and proteins. New York: Academic Press. pp. 377–397.
  89. Tlusty T (February 2008). "Rate-distortion scenario for the emergence and evolution of noisy molecular codes". Physical Review Letters. 100 (4): 048101. arXiv: 1007.4149 . Bibcode:2008PhRvL.100d8101T. doi:10.1103/PhysRevLett.100.048101. PMID   18352335. S2CID   12246664.
  90. Sella G, Ardell DH (September 2006). "The coevolution of genes and genetic codes: Crick's frozen accident revisited". Journal of Molecular Evolution. 63 (3): 297–313. Bibcode:2006JMolE..63..297S. doi:10.1007/s00239-004-0176-7. PMID   16838217. S2CID   1260806.
  91. Tlusty T (September 2010). "A colorful origin for the genetic code: information theory, statistical mechanics and the emergence of molecular codes". Physics of Life Reviews. 7 (3): 362–76. arXiv: 1007.3906 . Bibcode:2010PhLRv...7..362T. doi:10.1016/j.plrev.2010.06.002. PMID   20558115. S2CID   1845965.
  92. Jee J, Sundstrom A, Massey SE, Mishra B (November 2013). "What can information-asymmetric games tell us about the context of Crick's 'frozen accident'?". Journal of the Royal Society, Interface. 10 (88): 20130614. doi:10.1098/rsif.2013.0614. PMC   3785830 . PMID   23985735.
  93. Itzkovitz S, Alon U (2007). "The genetic code is nearly optimal for allowing additional information within protein-coding sequences". Genome Research. 17 (4): 405–412. doi:10.1101/gr.5987307. PMC   1832087 . PMID   17293451.

Further reading