Просмотр кода страницы Genetic code

{{Short description|Rules by which information encoded within genetic material is translated into proteins}}
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[[File:RNA-codon.svg|thumb|A series of codons in part of a [[messenger RNA]] (mRNA) molecule. Each codon consists of three [[nucleotide]]s, 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.]]
'''Genetic code''' is a set of rules used by living [[cell (biology)|cells]] to [[Translation (biology)|translate]] information encoded within genetic material ([[DNA]] or [[RNA]] sequences of nucleotide triplets or [[codon]]s) into [[protein]]s. Translation is accomplished by the [[ribosome]], which links [[proteinogenic amino acid]]s in an order specified by [[messenger RNA]] (mRNA), using [[transfer RNA]] (tRNA) molecules to carry amino acids and to read the mRNA three [[nucleotide]]s at a time. The genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries.

The codons specify which amino acid will be added next during [[protein biosynthesis]]. With some exceptions,<ref name="Turanov_2009">{{cite journal | vauthors = Turanov AA, Lobanov AV, Fomenko DE, Morrison HG, Sogin ML, Klobutcher LA, Hatfield DL, Gladyshev VN | title = Genetic code supports targeted insertion of two amino acids by one codon | journal = Science | volume = 323 | issue = 5911 | pages = 259–261 | date = January 2009 | pmid = 19131629 | pmc = 3088105 | doi = 10.1126/science.1164748 }}</ref> a three-nucleotide codon in a nucleic acid sequence specifies a single amino acid. The vast majority of [[gene]]s are encoded with a single scheme (see the [[Codon tables|RNA codon table]]). That scheme is often called the canonical or standard genetic code, or simply ''the'' genetic code, though [[#Variations|variant codes]] (such as in [[mitochondrion|mitochondria]]) exist.

==History==
[[File:GeneticCode21-version-2.svg|thumb|upright=1.5|The genetic code]]{{Further|Adaptor hypothesis}}
Efforts to understand how proteins are encoded began after [[Nucleic acid double helix|DNA's structure]] was discovered in 1953. The key discoverers, English biophysicist [[Francis Crick]] and American biologist [[James Watson]], working together at the [[Cavendish Laboratory]] of the University of Cambridge, hypothesied that information flows from DNA and that there is a link between DNA and proteins.<ref>{{cite journal | vauthors = Watson JD, Crick FH | title = Genetical implications of the structure of deoxyribonucleic acid | journal = Nature | volume = 171 | issue = 4361 | pages = 964–967 | date = May 1953 | pmid = 13063483 | doi = 10.1038/171964b0 | s2cid = 4256010 | bibcode = 1953Natur.171..964W }}</ref> Soviet-American physicist [[George Gamow]] was the first to give a workable scheme for protein synthesis from DNA.<ref name="Stegmann_2016">{{cite journal | vauthors = Stegmann UE | title = 'Genetic Coding' Reconsidered: An Analysis of Actual Usage | journal = The British Journal for the Philosophy of Science | volume = 67 | issue = 3 | pages = 707–730 | date = September 2016 | pmid = 27924115 | pmc = 4990703 | doi = 10.1093/bjps/axv007 }}</ref> He postulated that sets of three bases (triplets) must be employed to encode the 20 standard amino acids used by living cells to build proteins, which would allow a maximum of {{nowrap|4{{sup|3}} {{=}} 64}} amino acids (all permutations of the four bases, read three at a time).<ref name="Crick_1990">{{cite book | vauthors = Crick F | chapter = Chapter 8: The Genetic Code | title = What Mad Pursuit: A Personal View of Scientific Discovery | pages = 89–101 | date = 10 July 1990 | chapter-url = {{google books | plainurl = y | id = awoXBQAAQBAJ | page = 89}}|publisher=Basic Books|oclc=1020240407|isbn=978-0-465-09138-6}}{{Dead link|date=May 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> He named this DNA–protein interaction (the original genetic code) as the "diamond code".<ref name="Hayes_1998">{{Cite journal | vauthors = Hayes B | title = Computing Science: The Invention of the Genetic Code | journal = American Scientist | volume = 86 | issue = 1 | pages = 8–14 | date = 1998 | doi = 10.1511/1998.17.3338 | jstor = 27856930 | s2cid = 121907709 | issn = 0003-0996 }}</ref>

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 [[Translation (biology)|proteins were synthesised]] from genes. However, the club could have only 20 permanent members to represent each of the 20 amino acids; and four additional honorary members to represent the four nucleotides of DNA.<ref name="Strauss_2019">{{cite journal | vauthors = Strauss BS | title = Martynas Yčas: The "Archivist" of the RNA Tie Club | journal = Genetics | volume = 211 | issue = 3 | pages = 789–795 | date = March 2019 | pmid = 30846543 | pmc = 6404253 | doi = 10.1534/genetics.118.301754 }}</ref>

The first scientific contribution of the club, later recorded as "one of the most important unpublished articles in the history of science"<ref>{{Cite web | title = Francis Crick - Profiles in Science Search Results | url = https://profiles.nlm.nih.gov/spotlight/sc/catalog/nlm:nlmuid-101584582X73-doc | access-date = 2022-07-21 | website = profiles.nlm.nih.gov }}</ref> and "the most famous unpublished paper in the annals of molecular biology",<ref name="Fry_2022">{{Cite journal | vauthors = Fry M | title = Crick's Adaptor Hypothesis and the Discovery of Transfer RNA: Experiment Surpassing Theoretical Prediction | journal = Philosophy, Theory, and Practice in Biology | volume = 14 | date = 2022 | doi = 10.3998/ptpbio.2628 | url = https://journals.publishing.umich.edu/ptpbio/article/id/2628/ | issn = 2475-3025 | s2cid = 249112573 | doi-access = free }}</ref> was made by Crick. Crick presented a type-written paper titled  "On Degenerate Templates and the Adaptor Hypothesis: A Note for the RNA Tie Club"<ref name="Crick_1955">{{Cite web | vauthors = Crick F | title = On Degenerate Templates and the Adaptor Hypothesis: A Note for the RNA Tie Club | date = 1955 | url = https://collections.nlm.nih.gov/catalog/nlm:nlmuid-101584582X73-doc | archive-url = https://web.archive.org/web/20220816132804/https://collections.nlm.nih.gov/catalog/nlm:nlmuid-101584582X73-doc | archive-date = 16 August 2022 | access-date = 2022-07-21 | website = National Library of Medicine }}</ref> to the members of the club in January 1955, which "totally changed the way we thought about protein synthesis", as Watson recalled.<ref name="Watson_2007">{{Cite book | vauthors = Watson JD | title = Avoid Boring People: Lessons from a Life in Science | page = 112 | date = 2007 | url = https://books.google.com/books?id=mav7RvFfjDkC | publisher = Oxford University Press | isbn = 978-0-19-280273-6 | language = en | oclc = 47716375 }}</ref> The hypothesis states that the triplet code was not passed on to amino acids as Gamow thought, but carried by a different molecule, an adaptor, that interacts with amino acids.<ref name="Fry_2022" /> The adaptor was later identified as tRNA.<ref>{{cite journal | vauthors = Barciszewska MZ, Perrigue PM, Barciszewski J | title = tRNA--the golden standard in molecular biology | journal = Molecular Biosystems | volume = 12 | issue = 1 | pages = 12–17 | date = January 2016 | pmid = 26549858 | doi = 10.1039/c5mb00557d }}</ref>

===Codons===
{{Redirect|Codon}}
{{See also|DNA and RNA codon tables#Translation table 1}}

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

[[Marshall Nirenberg]] and [[J. Heinrich Matthaei]] were the first to reveal the nature of a codon in 1961.<ref>{{cite journal | vauthors = Yanofsky C | title = Establishing the triplet nature of the genetic code | journal = Cell | volume = 128 | issue = 5 | pages = 815–818 | date = March 2007 | pmid = 17350564 | doi = 10.1016/j.cell.2007.02.029 | s2cid = 14249277 | doi-access = free }}</ref> They used a [[cell-free system]] to [[translation (biology)|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]].<ref name="Nirenberg_1961">{{cite journal | vauthors = Nirenberg MW, Matthaei JH | title = The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 47 | issue = 10 | pages = 1588–1602 | date = October 1961 | pmid = 14479932 | pmc = 223178 | doi = 10.1073/pnas.47.10.1588 | doi-access = free | bibcode = 1961PNAS...47.1588N }}</ref> 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]]<ref name="Gardner_1962">{{cite journal | vauthors = Gardner RS, Wahba AJ, Basilio C, Miller RS, Lengyel P, Speyer JF | title = Synthetic polynucleotides and the amino acid code. VII | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 48 | issue = 12 | pages = 2087–2094 | date = December 1962 | pmid = 13946552 | pmc = 221128 | doi = 10.1073/pnas.48.12.2087 | doi-access = free | bibcode = 1962PNAS...48.2087G }}</ref> and that the poly-[[cytosine]] RNA sequence (CCCCC...) coded for the polypeptide poly-[[proline]].<ref name="Wahba_1963">{{cite journal | vauthors = Wahba AJ, Gardner RS, Basilio C, Miller RS, Speyer JF, Lengyel P | title = Synthetic polynucleotides and the amino acid code. VIII | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 49 | issue = 1 | pages = 116–122 | date = January 1963 | pmid = 13998282 | pmc = 300638 | doi = 10.1073/pnas.49.1.116 | doi-access = free | bibcode = 1963PNAS...49..116W }}</ref> 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.<ref name="Nobel_1959">{{cite press release | title = The Nobel Prize in Physiology or Medicine 1959 | date = 1959 | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1959/index.html | quote = 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'. | publisher = The Royal Swedish Academy of Science | access-date = 2010-02-27 }}</ref>

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 [[ribosome]]s, the components of cells that [[Translation (biology)|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.<ref name="Nirenberg_1965">{{cite journal | vauthors = Nirenberg M, Leder P, Bernfield M, Brimacombe R, Trupin J, Rottman F, O'Neal C | title = RNA codewords and protein synthesis, VII. On the general nature of the RNA code | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 53 | issue = 5 | pages = 1161–1168 | date = May 1965 | pmid = 5330357 | pmc = 301388 | doi = 10.1073/pnas.53.5.1161 | doi-access = free | bibcode = 1965PNAS...53.1161N }}</ref> Khorana, Holley and Nirenberg received the Nobel Prize (1968) for their work.<ref name="Nobel_1968">{{cite press release | title = The Nobel Prize in Physiology or Medicine 1968 | date = 1968 | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1968/index.html | quote = 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'. | publisher = The Royal Swedish Academy of Science | access-date = 2010-02-27 }}</ref>

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.<ref>{{cite journal | vauthors = Edgar B | title = The genome of bacteriophage T4: an archeological dig | journal = Genetics | volume = 168 | issue = 2 | pages = 575–582 | date = October 2004 | pmid = 15514035 | pmc = 1448817 | doi = 10.1093/genetics/168.2.575 }}</ref> The other two stop codons were named "ochre" and "opal" in order to keep the "color names" theme.

=== Expanded genetic codes (synthetic biology) ===
{{Main|Expanded genetic code}}
{{See also|Nucleic acid analogues}}

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.<ref>{{Cite book | vauthors = Budisa N | title = The book at the Wiley Online Library | date = 2005-12-23 | doi = 10.1002/3527607188 | isbn = 978-3-527-31243-6 }}</ref>
However, there are different opinions, concepts, approaches and ideas, which is the best way to change it experimentally.{{Clarify|reason=are the opinions differing on "which one method is the best to change the experiments"?|date=February 2025}} Even models are proposed that predict "entry points" for synthetic amino acid invasion of the genetic code.<ref>{{cite journal | vauthors = Kubyshkin V, Budisa N | title = Synthetic alienation of microbial organisms by using genetic code engineering: Why and how? | journal = Biotechnology Journal | volume = 12 | issue = 8 | page = 16000933 | date = August 2017 | article-number = 1600097 | pmid = 28671771 | doi = 10.1002/biot.201600097 }}</ref>

Since 2001, 40 non-natural amino acids have been added into proteins by creating a unique codon (recoding) and a corresponding transfer-RNA:aminoacyl&nbsp;– 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.<ref name="Xie_2005">{{cite journal | vauthors = Xie J, Schultz PG | title = Adding amino acids to the genetic repertoire | journal = Current Opinion in Chemical Biology | volume = 9 | issue = 6 | pages = 548–554 | date = December 2005 | pmid = 16260173 | doi = 10.1016/j.cbpa.2005.10.011 }}</ref><ref name="Wang_2009">{{cite journal | vauthors = Wang Q, Parrish AR, Wang L | title = Expanding the genetic code for biological studies | journal = Chemistry & Biology | volume = 16 | issue = 3 | pages = 323–336 | date = March 2009 | pmid = 19318213 | pmc = 2696486 | doi = 10.1016/j.chembiol.2009.03.001 }}</ref>

H. Murakami and M. Sisido extended some codons to have four and five bases. [[Steven A. Benner]] constructed a functional 65th (''[[in vivo]]'') codon.<ref name="Simon_2005">{{cite book | vauthors = Simon M | title = Emergent Computation: Emphasizing Bioinformatics | pages = 105–106 | date = 7 January 2005 | url = {{google books | plainurl = y | id = Uxg51oZNkIsC | page = 105}}|publisher=Springer Science & Business Media|isbn=978-0-387-22046-8}}</ref>

In 2015 [[Nediljko Budisa|N. Budisa]], [[Dieter Söll|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 [[Bacteria|bacterium]] ''[[Escherichia coli|E. coli]]''.<ref>{{cite journal | vauthors = Hoesl MG, Oehm S, Durkin P, Darmon E, Peil L, Aerni HR, Rappsilber J, Rinehart J, Leach D, Söll D, Budisa N | title = Chemical Evolution of a Bacterial Proteome | journal = Angewandte Chemie | volume = 54 | issue = 34 | pages = 10030–10034 | date = August 2015 | pmid = 26136259 | pmc = 4782924 | doi = 10.1002/anie.201502868 | bibcode = 2015ACIE...5410030H | author-link7 = Juri Rappsilber }} NIHMSID: NIHMS711205</ref>

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.<ref>{{cite web | title = First stable semisynthetic organism created | work =  Kurzweil Library |date=3 February 2017|url=http://www.kurzweilai.net/first-stable-semisynthetic-organism-created |access-date=2017-02-09}}</ref><ref>{{cite journal | vauthors = Zhang Y, Lamb BM, Feldman AW, Zhou AX, Lavergne T, Li L, Romesberg FE | title = A semisynthetic organism engineered for the stable expansion of the genetic alphabet | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 6 | pages = 1317–1322 | date = February 2017 | pmid = 28115716 | pmc = 5307467 | doi = 10.1073/pnas.1616443114 | doi-access = free | bibcode = 2017PNAS..114.1317Z }}</ref>

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.<ref>{{cite journal | vauthors = Han S, Yang A, Lee S, Lee HW, Park CB, Park HS | title = Expanding the genetic code of Mus musculus | journal = Nature Communications | volume = 8 | date = February 2017 | pmid = 28220771 | pmc = 5321798 | doi = 10.1038/ncomms14568 | bibcode = 2017NatCo...814568H | article-number = 14568 }}</ref>

In May 2019, researchers reported the creation of a new "Syn61" strain of the ''E. coli'' bacteria. This strain has a fully [[Synthetic biology#Synthetic life|synthetic]] genome that is refactored (all overlaps expanded), recoded (removing the use of three out of 64 codons completely), and further modified to remove the now unnecessary tRNAs and release factors. It is fully [[Genetic viability|viable]] and grows 1.6× slower than its wild-type counterpart "[[Escherichia coli#MDS42|MDS42]]".<ref name="Zimmer_2019">{{cite news | vauthors = Zimmer C | title = 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. | date = 15 May 2019 | url = https://www.nytimes.com/2019/05/15/science/synthetic-genome-bacteria.html | archive-url = https://ghostarchive.org/archive/20220102/https://www.nytimes.com/2019/05/15/science/synthetic-genome-bacteria.html | archive-date = 2022-01-02 | url-access = limited | url-status = live | work = [[The New York Times]] | access-date = 16 May 2019 }}{{cbignore}}</ref><ref name="Fredens_2019">{{cite journal | vauthors = Fredens J, Wang K, de la Torre D, Funke LF, Robertson WE, Christova Y, Chia T, Schmied WH, Dunkelmann DL, Beránek V, Uttamapinant C, Llamazares AG, Elliott TS, Chin JW | title = Total synthesis of Escherichia coli with a recoded genome | journal = Nature | volume = 569 | issue = 7757 | pages = 514–518 | date = May 2019 | pmid = 31092918 | pmc = 7039709 | doi = 10.1038/s41586-019-1192-5 | s2cid = 205571025 | bibcode = 2019Natur.569..514F }}</ref>

In 2025, researchers reported a new "Syn57" strain, which removes the use of 7 out of 64 codons completely.<ref>{{cite journal | vauthors = Robertson WE, Rehm FB, Spinck M, Schumann RL, Tian R, Liu W, Gu Y, Kleefeldt AA, Day CF, Liu KC, Christova Y, Zürcher JF, Böge FL, Birnbaum J, van Bijsterveldt L, Chin JW | title = ''Escherichia coli'' with a 57-codon genetic code | journal = Science | article-number = eady4368 | date = July 2025 | volume = 390 | issue = 6771 | pmid = 40743368 | doi = 10.1126/science.ady4368 | biorxiv = 10.1101/2025.05.02.651837 | doi-access = free }}</ref>

==Features==
[[File:Homo sapiens-mtDNA~NC 012920-ATP8+ATP6 Overlap.svg|thumb|right|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<ref name="NCBI NC_012920">''Homo sapiens'' mitochondrion, complete genome. [https://www.ncbi.nlm.nih.gov/nuccore/NC_012920.1 "Revised Cambridge Reference Sequence (rCRS): accession NC_012920"], ''[[National Center for Biotechnology Information]]''. Retrieved on 27 December 2017.</ref>). 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===
{{Main|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' to 3'|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.<ref name="genetics_ dictionary"/>{{rp|330}} Protein-coding frames are defined by a [[start codon]], usually the first AUG codon in the RNA, (ATG in DNA) sequence.

In [[eukaryote]]s, open reading frames in [[exon]]s are often interrupted by [[intron]]s.

=== 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 ''[[Escherichia coli|E. coli]]'' and [[initiation factor]]s are also required to start translation. The most common start codon is AUG, which is read as [[methionine]] or as [[N-Formylmethionine|formylmethionine]] (in bacteria, mitochondria, and plastids). 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.<ref name="Touriol_2003">{{cite journal | vauthors = Touriol C, Bornes S, Bonnal S, Audigier S, Prats H, Prats AC, Vagner S | title = Generation of protein isoform diversity by alternative initiation of translation at non-AUG codons | journal = Biology of the Cell | volume = 95 | issue = 3–4 | pages = 169–178 | date = 2003 | pmid = 12867081 | doi = 10.1016/S0248-4900(03)00033-9 | doi-access = free }}</ref>

The three [[stop codon]]s 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.<ref name="urlHow nonsense mutations got their names">{{cite web | vauthors = Maloy S | title = How nonsense mutations got their names | date = 2003-11-29 | url = http://www.sci.sdsu.edu/~smaloy/MicrobialGenetics/topics/rev-sup/amber-name.html | archive-url = http://web.archive.org/web/20220310032422/http://www.sci.sdsu.edu/~smaloy/MicrobialGenetics/topics/rev-sup/amber-name.html | archive-date = 10 March 2022 | work = Microbial Genetics Course | publisher = San Diego State University | access-date = 2010-03-10 }}</ref>

===Effect of mutations===
[[File:Notable mutations.svg|upright=1.75|thumb|Examples of notable [[mutation]]s that can occur in humans<ref>References for the image are found in Wikimedia Commons page at: [[Commons:File:Notable mutations.svg#References]].</ref>]]<!-- EXPANSION OF THE IMAGE WITH MORE EXAMPLES IS EXPECTED (see its discussion page)-->

During the process of [[DNA replication]], errors occasionally occur in the [[polymerization]] of the second strand. These errors, [[mutation]]s, 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&nbsp;million bases—due to the "[[Proofreading (biology)|proofreading]]" ability of [[DNA polymerase]]s.<ref name="griffiths2000sect2706">{{cite book | chapter = Spontaneous mutations | title = An Introduction to Genetic Analysis | location = New York | date = 2000 | veditors = Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gelbart | isbn = 978-0-7167-3520-5 | edition = 7th | publisher = W. H. Freeman | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.2706 }}</ref><ref name="Freisinger_2004">{{cite journal | vauthors = Freisinger E, Grollman AP, Miller H, Kisker C | title = Lesion (in)tolerance reveals insights into DNA replication fidelity | journal = The EMBO Journal | volume = 23 | issue = 7 | pages = 1494–1505 | date = April 2004 | pmid = 15057282 | pmc = 391067 | doi = 10.1038/sj.emboj.7600158 }}</ref>

[[Missense mutation]]s and [[nonsense mutation]]s are examples of [[point mutation]]s that  can cause genetic diseases such as [[sickle-cell disease]] and [[thalassemia]] respectively.<ref name="Chang_1979">{{cite journal | vauthors = Chang JC, Kan YW | title = beta 0 thalassemia, a nonsense mutation in man | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 76 | issue = 6 | pages = 2886–2889 | date = June 1979 | pmid = 88735 | pmc = 383714 | doi = 10.1073/pnas.76.6.2886 | doi-access = free | bibcode = 1979PNAS...76.2886C }}</ref><ref name="Boillee_2006">{{cite journal | vauthors = Boillée S, Vande Velde C, Cleveland DW | title = ALS: a disease of motor neurons and their nonneuronal neighbors | journal = Neuron | volume = 52 | issue = 1 | pages = 39–59 | date = October 2006 | pmid = 17015226 | doi = 10.1016/j.neuron.2006.09.018 | doi-access = free }}</ref> 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]].<ref name="genetics_ dictionary">{{cite book | vauthors = King RC, Mulligan P, Stansfield W | title = A Dictionary of Genetics | page = 608 | date = 10 January 2013 | url = {{google books | plainurl = y | id = 5jhH0HTjEdkC}}|publisher=OUP USA|isbn=978-0-19-976644-4}}</ref>

Mutations that disrupt the reading frame sequence by [[indels]] ([[gene insertion|insertions]] or [[genetic deletion|deletions]]) of a non-multiple of 3 nucleotide bases are known as [[frameshift mutation]]s. 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.<ref name="Isbrandt_1996">{{cite journal | vauthors = Isbrandt D, Hopwood JJ, von Figura K, Peters C | title = Two novel frameshift mutations causing premature stop codons in a patient with the severe form of Maroteaux-Lamy syndrome | journal = Human Mutation | volume = 7 | issue = 4 | pages = 361–363 | date = 1996 | pmid = 8723688 | doi = 10.1002/(SICI)1098-1004(1996)7:4<361::AID-HUMU12>3.0.CO;2-0 | s2cid = 22693748 | doi-access = free }}</ref> 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.<ref name="Crow_1993">{{cite journal | vauthors = Crow JF | title = How much do we know about spontaneous human mutation rates? | journal = Environmental and Molecular Mutagenesis | volume = 21 | issue = 2 | pages = 122–129 | date = 1993 | pmid = 8444142 | doi = 10.1002/em.2850210205 | s2cid = 32918971 | bibcode = 1993EnvMM..21..122C }}</ref> Frameshift mutations may result in severe genetic diseases such as [[Tay–Sachs disease]].<ref name="Lewis_2005">{{cite book | vauthors = Lewis R | title = Human Genetics: Concepts and Applications | location = Boston, Mass | pages = 227–228 | date = 2005 | edition = 6th | publisher = McGraw Hill | isbn = 978-0-07-111156-0 }}</ref>

Although most mutations that change protein sequences are harmful or neutral, some mutations have benefits.<ref>{{cite journal | vauthors = Sawyer SA, Parsch J, Zhang Z, Hartl DL | title = Prevalence of positive selection among nearly neutral amino acid replacements in Drosophila | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 16 | pages = 6504–6510 | date = April 2007 | pmid = 17409186 | pmc = 1871816 | doi = 10.1073/pnas.0701572104 | doi-access = free | bibcode = 2007PNAS..104.6504S }}</ref> 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]].<ref>{{cite journal | vauthors = KR B | title = Malaria and the Red Cell | journal = Harvard | date = 2002 | url = http://sickle.bwh.harvard.edu/malaria_sickle.html | archive-url = https://web.archive.org/web/20111127201806/http://sickle.bwh.harvard.edu/malaria_sickle.html | archive-date = 27 November 2011 }}</ref> [[Virus]]es that use [[RNA]] as their genetic material have rapid mutation rates,<ref>{{cite journal | vauthors = Drake JW, Holland JJ | title = Mutation rates among RNA viruses | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 24 | pages = 13910–13913 | date = November 1999 | pmid = 10570172 | pmc = 24164 | doi = 10.1073/pnas.96.24.13910 | doi-access = free | bibcode = 1999PNAS...9613910D }}</ref> which can be an advantage, since these viruses thereby evolve rapidly, and thus evade the [[immune system]] defensive responses.<ref>{{cite journal | vauthors = Holland J, Spindler K, Horodyski F, Grabau E, Nichol S, VandePol S | title = Rapid evolution of RNA genomes | journal = Science | volume = 215 | issue = 4540 | pages = 1577–1585 | date = March 1982 | pmid = 7041255 | doi = 10.1126/science.7041255 | bibcode = 1982Sci...215.1577H }}</ref> 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.<ref>{{cite journal | vauthors = de Visser JA, Rozen DE | title = Clonal interference and the periodic selection of new beneficial mutations in Escherichia coli | journal = Genetics | volume = 172 | issue = 4 | pages = 2093–2100 | date = April 2006 | pmid = 16489229 | pmc = 1456385 | doi = 10.1534/genetics.105.052373 }}</ref>

===Degeneracy===
{{Main|Codon degeneracy}}
[[File:Genetic Code Simple Corrected.pdf|thumb|Grouping of codons by amino acid residue molar volume and [[hydropathicity]].  A [[:File:ELLIPTICAL GENETIC CODE Ian.png|more detailed version]] is available.]]
[[File:3D Genetic Code.jpg|thumb|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 [[Amino acid#Table of standard amino acid abbreviations and properties|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 [[DNA and RNA codon tables|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 '''Y'''U'''R''' or CU'''N''' (UUA, UUG, CUU, CUC, CUA, or CUG) codons (difference in the first or third position indicated using [[Nucleic acid notation|IUPAC notation]]), while the amino acid [[serine]] is specified by UC'''N''' or AG'''Y''' (UCA, UCG, UCC, UCU, AGU, or AGC) codons (difference in the first, second, or third position).<ref name="Watson_2008">{{cite book | vauthors = Watson JD | title = Molecular Biology of the Gene | year = 2008 | url = {{google books | plainurl = y | id = MByWPwAACAAJ}}|publisher=Pearson/Benjamin Cummings|isbn=978-0-8053-9592-1}} {{rp|[{{google books |plainurl=y |id=MByWPwAACAAJ|page=102}} 102–117]}} {{rp|[{{google books |plainurl=y |id=MByWPwAACAAJ|page=521}} 521–522]}}</ref> 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|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.''<ref name="MichelBeyerle_1990">{{cite book | vauthors = Michel-Beyerle ME | title = Reaction centers of photosynthetic bacteria: Feldafing-II-Meeting | year = 1990 | url = {{google books | plainurl = y | id = xD5OAQAAIAAJ}}|publisher=Springer-Verlag|isbn=978-3-540-53420-4}}</ref><ref>Füllen G, Youvan DC (1994). "Genetic Algorithms and Recursive Ensemble Mutagenesis in Protein Engineering". Complexity International 1.</ref>  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.<ref name="Fricke_2019">{{cite journal | vauthors = Fricke M, Gerst R, Ibrahim B, Niepmann M, Marz M | title = Global importance of RNA secondary structures in protein-coding sequences | journal = Bioinformatics | volume = 35 | issue = 4 | pages = 579–583 | date = February 2019 | pmid = 30101307 | pmc = 7109657 | doi = 10.1093/bioinformatics/bty678 | s2cid = 51968530 }}</ref>  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.<ref name="Fricke_2019" />

===Codon usage bias===
{{Main|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 (biology)|translation]]. The codon varies by organism; for example, most common proline codon in E. coli is CCG, whereas in humans this is the least used proline codon.<ref>{{Cite web | title = Codon Usage Frequency Table(chart)-Genscript | url = https://www.genscript.com/tools/codon-frequency-table | access-date = 2022-02-04 | website = www.genscript.com }}</ref>

{{collapse top|title=Human genome codon frequency table<ref>{{Cite web | title = Codon usage table | url = http://www.kazusa.or.jp/codon/cgi-bin/showcodon.cgi?species=9606&aa=1&style=N | website = www.kazusa.or.jp }}</ref>}}
{|class="wikitable" style="text-align: center;"
|-
!Codon || AA{{ref label|start|C|C}} || Fraction{{ref label|start|D|D}} || Freq [[per thousand|‰]]{{ref label|start|E|E}} || Number{{ref label|start|F|F}}
|rowspan=17|
!Codon || AA || Fraction || Freq [[per thousand|‰]] || Number
|rowspan=17|
!Codon || AA || Fraction || Freq [[per thousand|‰]] || Number 
|rowspan=17|
!Codon || AA || Fraction || Freq [[per thousand|‰]] || Number 
|-
|UUU||F||0.46||17.6||714,298||UCU||S||0.19||15.2||618,711||UAU||Y||0.44||12.2||495,699||UGU||C||0.46||10.6||430,311
|-
|UUC||F||0.54||20.3||824,692||UCC||S||0.22||17.7||718,892||UAC||Y||0.56||15.3||622,407||UGC||C||0.54||12.6||513,028
|-
|UUA||L||0.08||7.7||311,881||UCA||S||0.15||12.2||496,448||UAA||*||0.30||1.0||40,285||UGA||*||0.47||1.6||63,237
|-
|UUG||L||0.13||12.9||525,688||UCG||S||0.05||4.4||179,419||UAG||*||0.24||0.8||32,109||UGG||W||1.00||13.2||535,595
|-
|CUU||L||0.13||13.2||536,515||CCU||P||0.29||17.5||713,233||CAU||H||0.42||10.9||441,711||CGU||R||0.08||4.5||184,609
|-
|CUC||L||0.20||19.6||796,638||CCC||P||0.32||19.8||804,620||CAC||H||0.58||15.1||613,713||CGC||R||0.18||10.4||423,516
|-
|CUA||L||0.07||7.2||290,751||CCA||P||0.28||16.9||688,038||CAA||Q||0.27||12.3||501,911||CGA||R||0.11||6.2||250,760
|-
|CUG||L||0.40||39.6||1,611,801||CCG||P||0.11||6.9||281,570||CAG||Q||0.73||34.2||1,391,973||CGG||R||0.20||11.4||464,485
|-
|AUU||I||0.36||16.0||650,473||ACU||T||0.25||13.1||533,609||AAU||N||0.47||17.0||689,701||AGU||S||0.15||12.1||493,429
|-
|AUC||I||0.47||20.8||846,466||ACC||T||0.36||18.9||768,147||AAC||N||0.53||19.1||776,603||AGC||S||0.24||19.5||791,383
|-
|AUA||I||0.17||7.5||304,565||ACA||T||0.28||15.1||614,523||AAA||K||0.43||24.4||993,621||AGA||R||0.21||12.2||494,682
|-
|AUG||M||1.00||22.0||896,005||ACG||T||0.11||6.1||246,105||AAG||K||0.57||31.9||1,295,568||AGG||R||0.21||12.0||486,463
|-
|GUU||V||0.18||11.0||448,607||GCU||A||0.27||18.4||750,096||GAU||D||0.46||21.8||885,429||GGU||G||0.16||10.8||437,126
|-
|GUC||V||0.24||14.5||588,138||GCC||A||0.40||27.7||1,127,679||GAC||D||0.54||25.1||1,020,595||GGC||G||0.34||22.2||903,565
|-
|GUA||V||0.12||7.1||287,712||GCA||A||0.23||15.8||643,471||GAA||E||0.42||29.0||1,177,632||GGA||G||0.25||16.5||669,873
|-
|GUG||V||0.46||28.1||1,143,534||GCG||A||0.11||7.4||299,495||GAG||E||0.58||39.6||1,609,975||GGG||G||0.25||16.5||669,768
|}
{{collapse bottom}}

==Alternative genetic codes==
{{See also|DNA and RNA codon tables#Alternative codons}}

=== 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.<ref name="Zhang2005" /> Both selenocysteine and pyrrolysine may be present in the same organism.<ref name=Zhang2005>{{cite journal | vauthors = Zhang Y, Baranov PV, Atkins JF, Gladyshev VN | title = Pyrrolysine and selenocysteine use dissimilar decoding strategies | journal = The Journal of Biological Chemistry | volume = 280 | issue = 21 | pages = 20740–20751 | date = May 2005 | pmid = 15788401 | doi = 10.1074/jbc.M501458200 | doi-access = free }}</ref> 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.<ref name="Prat_2012">{{cite journal | vauthors = Prat L, Heinemann IU, Aerni HR, Rinehart J, O'Donoghue P, Söll D | title = Carbon source-dependent expansion of the genetic code in bacteria | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 51 | pages = 21070–21075 | date = December 2012 | pmid = 23185002 | pmc = 3529041 | doi = 10.1073/pnas.1218613110 | doi-access = free | bibcode = 2012PNAS..10921070P }}</ref>

=== Variations ===
{{See also|List of genetic codes}}
[[File:FACIL genetic code logo.png|thumb|upright=2.3|Genetic code [[sequence logo|logo]] of the ''Globobulimina pseudospinescens'' mitochondrial genome by FACIL. The program is able to correctly infer that the [[The mold, protozoan, and coelenterate mitochondrial code and the mycoplasma/spiroplasma code|Protozoan Mitochondrial Code]] is in use.<ref name="Dutilh_2011" /> 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.]]
There was originally a simple and widely accepted argument that the genetic code should be universal: namely, that any variation in the genetic code would be lethal to the organism (although Crick had stated that viruses were an exception). This is known as the "frozen accident" argument for the universality of the genetic code. However, in his seminal paper on the origins of the genetic code in 1968, Francis Crick still stated that the universality of the genetic code in all organisms was an unproven assumption, and was probably not true in some instances. He predicted that "The code is universal (the same in all organisms) or nearly so".<ref name = "Crick_1968">{{cite journal | vauthors = Crick FH | title = The origin of the genetic code | journal = Journal of Molecular Biology | volume = 38 | issue = 3 | pages = 367–379 | date = December 1968 | pmid = 4887876 | doi = 10.1016/0022-2836(68)90392-6 }}</ref> The first variation was discovered in 1979, by researchers studying [[human mitochondrial genetics|human mitochondrial genes]].<ref>
{{cite journal | vauthors = Barrell BG, Bankier AT, Drouin J | title = A different genetic code in human mitochondria | journal = Nature | volume = 282 | issue = 5735 | pages = 189–194 | date = November 1979 | pmid = 226894 | doi = 10.1038/282189a0 | bibcode = 1979Natur.282..189B | s2cid = 4335828 }} ([https://www.ncbi.nlm.nih.gov/pubmed/226894])</ref> Many slight variants were discovered thereafter,<ref name="Elzanowski_2008" /> including various alternative mitochondrial codes.<ref>{{cite journal | vauthors = Jukes TH, Osawa S | title = The genetic code in mitochondria and chloroplasts | journal = Experientia | volume = 46 | issue = 11–12 | pages = 1117–1126 | date = December 1990 | pmid = 2253709 | doi = 10.1007/BF01936921 | s2cid = 19264964 }}</ref> 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]]'').<ref>{{cite journal | vauthors = Fitzpatrick DA, Logue ME, Stajich JE, Butler G | title = A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis | journal = BMC Evolutionary Biology | volume = 6 | page = 99 | date = November 2006 | pmid = 17121679 | pmc = 1679813 | doi = 10.1186/1471-2148-6-99 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Santos MA, Tuite MF | title = The CUG codon is decoded in vivo as serine and not leucine in Candida albicans | journal = Nucleic Acids Research | volume = 23 | issue = 9 | pages = 1481–1486 | date = May 1995 | pmid = 7784200 | pmc = 306886 | doi = 10.1093/nar/23.9.1481 }}</ref><ref>{{cite journal | vauthors = Butler G, Rasmussen MD, Lin MF, Santos MA, Sakthikumar S, Munro CA, Rheinbay E, Grabherr M, Forche A, Reedy JL, Agrafioti I, Arnaud MB, Bates S, Brown AJ, Brunke S, Costanzo MC, Fitzpatrick DA, de Groot PW, Harris D, Hoyer LL, Hube B, Klis FM, Kodira C, Lennard N, Logue ME, Martin R, Neiman AM, Nikolaou E, Quail MA, Quinn J, Santos MC, Schmitzberger FF, Sherlock G, Shah P, Silverstein KA, Skrzypek MS, Soll D, Staggs R, Stansfield I, Stumpf MP, Sudbery PE, Srikantha T, Zeng Q, Berman J, Berriman M, Heitman J, Gow NA, Lorenz MC, Birren BW, Kellis M, Cuomo CA | title = Evolution of pathogenicity and sexual reproduction in eight Candida genomes | journal = Nature | volume = 459 | issue = 7247 | pages = 657–662 | date = June 2009 | pmid = 19465905 | pmc = 2834264 | doi = 10.1038/nature08064 | bibcode = 2009Natur.459..657B }}</ref> 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 [[totivirus]]es have adapted to the host's genetic code modification.<ref name="Taylor_2013">{{cite journal | vauthors = Taylor DJ, Ballinger MJ, Bowman SM, Bruenn JA | title = Virus-host co-evolution under a modified nuclear genetic code | journal = PeerJ | volume = 1 | article-number = e50 | date = 2013 | pmid = 23638388 | pmc = 3628385 | doi = 10.7717/peerj.50 | doi-access = free }}</ref> In [[bacteria]] and [[archaea]], GUG and UUG are common start codons. In rare cases, certain proteins may use alternative start codons.<ref name="Elzanowski_2008">{{cite web | vauthors = Elzanowski A, Ostell J | title = The Genetic Codes | date = 2008-04-07 | url = https://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi?mode=c | publisher = National Center for Biotechnology Information (NCBI) | access-date = 2010-03-10 }}</ref>
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.<ref name="Hofhuis_2016">{{cite journal | vauthors = Hofhuis J, Schueren F, Nötzel C, Lingner T, Gärtner J, Jahn O, Thoms S | title = The functional readthrough extension of malate dehydrogenase reveals a modification of the genetic code | journal = Open Biology | volume = 6 | issue = 11 | article-number = 160246 | date = November 2016 | pmid = 27881739 | pmc = 5133446 | doi = 10.1098/rsob.160246 }}</ref> This type of recoding is induced by a high-readthrough stop codon context<ref name="Schueren_2014">{{cite journal | vauthors = Schueren F, Lingner T, George R, Hofhuis J, Dickel C, Gärtner J, Thoms S | title = Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals | journal = eLife | volume = 3 | article-number = e03640 | date = September 2014 | pmid = 25247702 | pmc = 4359377 | doi = 10.7554/eLife.03640 | doi-access = free }}</ref> and it is referred to as ''functional translational readthrough''.<ref name="Schueren_2016">{{cite journal | vauthors = Schueren F, Thoms S | title = Functional Translational Readthrough: A Systems Biology Perspective | journal = PLOS Genetics | volume = 12 | issue = 8 | article-number = e1006196 | date = August 2016 | pmid = 27490485 | pmc = 4973966 | doi = 10.1371/journal.pgen.1006196 | doi-access = free }}</ref>

Despite these differences, all known naturally occurring codes are very similar. The coding mechanism is the same for all organisms: three-base codons, [[Transfer RNA|tRNA]], ribosomes, single direction reading and translating single codons into single amino acids.<ref>{{cite journal | vauthors = Kubyshkin V, Acevedo-Rocha CG, Budisa N | title = On universal coding events in protein biogenesis | journal = Bio Systems | volume = 164 | pages = 16–25 | date = February 2018 | pmid = 29030023 | doi = 10.1016/j.biosystems.2017.10.004 | doi-access = free | bibcode = 2018BiSys.164...16K }}</ref> 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''<ref>{{cite journal | vauthors = Heaphy SM, Mariotti M, Gladyshev VN, Atkins JF, Baranov PV | title = Novel Ciliate Genetic Code Variants Including the Reassignment of All Three Stop Codons to Sense Codons in Condylostoma magnum | journal = Molecular Biology and Evolution | volume = 33 | issue = 11 | pages = 2885–2889 | date = November 2016 | pmid = 27501944 | pmc = 5062323 | doi = 10.1093/molbev/msw166 }}</ref> or trigger [[ribosomal frameshift]]ing as in ''[[Euplotes]]''.<ref>{{cite journal | vauthors = Lobanov AV, Heaphy SM, Turanov AA, Gerashchenko MV, Pucciarelli S, Devaraj RR, Xie F, Petyuk VA, Smith RD, Klobutcher LA, Atkins JF, Miceli C, Hatfield DL, Baranov PV, Gladyshev VN | title = Position-dependent termination and widespread obligatory frameshifting in Euplotes translation | journal = Nature Structural & Molecular Biology | volume = 24 | issue = 1 | pages = 61–68 | date = January 2017 | pmid = 27870834 | pmc = 5295771 | doi = 10.1038/nsmb.3330 }}</ref>

The origins and variation of the genetic code, including the mechanisms behind the evolvability of the genetic code, have been widely studied,<ref>{{cite journal | vauthors = Koonin EV, Novozhilov AS | title = Origin and evolution of the genetic code: the universal enigma | journal = IUBMB Life | volume = 61 | issue = 2 | pages = 99–111 | date = February 2009 | pmid = 19117371 | pmc = 3293468 | doi = 10.1002/iub.146 }}</ref><ref name="Pathways of Genetic Code Evolution">{{cite journal | vauthors = Sengupta S, Higgs PG | title = Pathways of Genetic Code Evolution in Ancient and Modern Organisms | journal = Journal of Molecular Evolution | volume = 80 | issue = 5–6 | pages = 229–243 | date = June 2015 | pmid = 26054480 | doi = 10.1007/s00239-015-9686-8 | s2cid = 15542587 | bibcode = 2015JMolE..80..229S }}</ref> and some studies have been done experimentally evolving the genetic code of some organisms.<ref>{{cite journal | vauthors = Xie J, Schultz PG | title = A chemical toolkit for proteins--an expanded genetic code | journal = Nature Reviews. Molecular Cell Biology | volume = 7 | issue = 10 | pages = 775–782 | date = October 2006 | pmid = 16926858 | doi = 10.1038/nrm2005 | s2cid = 19385756 }}</ref><ref>{{cite journal | vauthors = Liu CC, Schultz PG | title = Adding new chemistries to the genetic code | journal = Annual Review of Biochemistry | volume = 79 | pages = 413–444 | date = 2010 | pmid = 20307192 | doi = 10.1146/annurev.biochem.052308.105824 }}</ref><ref>{{cite journal | vauthors = Chin JW | title = Expanding and reprogramming the genetic code of cells and animals | journal = Annual Review of Biochemistry | volume = 83 | pages = 379–408 | date = February 2014 | pmid = 24555827 | doi = 10.1146/annurev-biochem-060713-035737 }}</ref>

=== Inference ===
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 infers a genetic code by searching which amino acids in homologous protein domains are most often aligned to every codon. The resulting amino acid (or stop codon) probabilities for each codon are displayed in a genetic code logo.<ref name="Dutilh_2011">{{cite journal | vauthors = 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 | title = FACIL: Fast and Accurate Genetic Code Inference and Logo | journal = Bioinformatics | volume = 27 | issue = 14 | pages = 1929–1933 | date = July 2011 | pmid = 21653513 | pmc = 3129529 | doi = 10.1093/bioinformatics/btr316 }}</ref>

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. This tool uses a similar approach to FACIL with a larger [[Pfam]] database. 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.<ref>{{cite journal | vauthors = Shulgina Y, Eddy SR | title = A computational screen for alternative genetic codes in over 250,000 genomes | journal = eLife | volume = 10 | date = November 2021 | article-number = e71402 | pmid = 34751130 | pmc = 8629427 | doi = 10.7554/eLife.71402 | doi-access = free }}</ref> Codetta was later used to analyze genetic code change in [[ciliates]].<ref>{{cite journal | vauthors = Chen W, Geng Y, Zhang B, Yan Y, Zhao F, Miao M | title = Stop or Not: Genome-Wide Profiling of Reassigned Stop Codons in Ciliates | journal = Molecular Biology and Evolution | volume = 40 | issue = 4 | date = April 2023 | article-number = msad064 | pmid = 36952281 | pmc = 10089648 | doi = 10.1093/molbev/msad064 }}</ref>

==Origin==
The genetic code is a key part of the [[origin of life|history of life]]. Under the [[RNA world hypothesis]], self-replicating RNA molecules preceded significant use of proteins. Under the nucleopeptide world hypothesis, significant use of peptides preceded the genetic code and was concurrent with early life's sophisticated use of RNA.<ref>{{cite journal | vauthors = Fried SD, Fujishima K, Makarov M, Cherepashuk I, Hlouchova K | title = Peptides before and during the nucleotide world: an origins story emphasizing cooperation between proteins and nucleic acids | journal = Journal of the Royal Society, Interface | volume = 19 | issue = 187 | article-number = 20210641 | date = February 2022 | pmid = 35135297 | pmc = 8833103 | doi = 10.1098/rsif.2021.0641 }}</ref> Transfer RNA molecules appear to have evolved before modern [[aminoacyl-tRNA synthetase]]s.<ref name="Ribas_de_Pouplana_1998">{{cite journal | vauthors = Ribas de Pouplana L, Turner RJ, Steer BA, Schimmel P | title = Genetic code origins: tRNAs older than their synthetases? | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 19 | pages = 11295–11300 | date = September 1998 | pmid = 9736730 | pmc = 21636 | doi = 10.1073/pnas.95.19.11295 | doi-access = free | bibcode = 1998PNAS...9511295D }}</ref> It is possible that synthetases replaced an earlier system of [[ribozyme]]s (RNA enzymes), or that amino acids were recognized by unique pockets in the tertiary structure of proto-tRNAs.<ref>{{cite journal | vauthors = Koonin EV | title = Frozen Accident Pushing 50: Stereochemistry, Expansion, and Chance in the Evolution of the Genetic Code | journal = Life | volume = 7 | issue = 2 | page = 22 | date = May 2017 | pmid = 28545255 | pmc = 5492144 | doi = 10.3390/life7020022 | doi-access = free | bibcode = 2017Life....7...22K }}</ref> It is not known why the genetic code only uses L-amino acids and not D-amino acids.<ref name="Erives_2011">{{cite journal | vauthors = Erives A | title = A model of proto-anti-codon RNA enzymes requiring L-amino acid homochirality | journal = Journal of Molecular Evolution | volume = 73 | issue = 1–2 | pages = 10–22 | date = August 2011 | pmid = 21779963 | pmc = 3223571 | doi = 10.1007/s00239-011-9453-4 | bibcode = 2011JMolE..73...10E }}</ref>

Any evolutionary model for the code's origin must account for its [[Robustness (evolution)|robustness]] of encoded proteins to errors during DNA replication and during translation. Many single nucleotide errors are [[Synonymous substitution|synonymous]], and those that are not tend to cause the [[Conservative replacement|substitution of a biochemically similar amino acid]]. Even holding the structure of the code the same such that clusters of codons encode the same amino acid, which amino acids are encoded by which sets of codons is "one in a million" with respect to robustness.<ref name="Freeland_1998">{{cite journal | vauthors = Freeland SJ, Hurst LD | title = The genetic code is one in a million | journal = Journal of Molecular Evolution | volume = 47 | issue = 3 | pages = 238–248 | date = September 1998 | pmid = 9732450 | doi = 10.1007/PL00006381 | s2cid = 20130470 | bibcode = 1998JMolE..47..238F }}</ref> Biochemically similar amino acids tend to share the same middle nucleotide, while synonymous changes generally happen at the third nucleotide.

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.<ref name="Taylor_1989">{{cite journal | vauthors = Taylor FJ, Coates D | title = The code within the codons | journal = Bio Systems | volume = 22 | issue = 3 | pages = 177–187 | date = 1989 | pmid = 2650752 | doi = 10.1016/0303-2647(89)90059-2 | bibcode = 1989BiSys..22..177T }}</ref> 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,<ref name="Di_Giulio_1989">{{cite journal | vauthors = Di Giulio M | title = The extension reached by the minimization of the polarity distances during the evolution of the genetic code | journal = Journal of Molecular Evolution | volume = 29 | issue = 4 | pages = 288–293 | date = October 1989 | pmid = 2514270 | doi = 10.1007/BF02103616 | s2cid = 20803686 | bibcode = 1989JMolE..29..288D }}</ref><ref name="Wong_1980">{{cite journal | vauthors = Wong JT | title = Role of minimization of chemical distances between amino acids in the evolution of the genetic code | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 77 | issue = 2 | pages = 1083–1086 | date = February 1980 | pmid = 6928661 | pmc = 348428 | doi = 10.1073/pnas.77.2.1083 | doi-access = free | bibcode = 1980PNAS...77.1083W }}</ref> reducing the problems caused by point mutations and mistranslations.<ref name="Freeland_1998" />

Three main hypotheses address the origin of the genetic code. Many models belong to one of them or to a hybrid:<ref name="Freeland_2000">{{cite journal | vauthors = Freeland SJ, Knight RD, Landweber LF, Hurst LD | title = Early fixation of an optimal genetic code | journal = Molecular Biology and Evolution | volume = 17 | issue = 4 | pages = 511–518 | date = April 2000 | pmid = 10742043 | doi = 10.1093/oxfordjournals.molbev.a026331 | doi-access = free }}</ref>

*Random freeze: the genetic code was randomly created. For example, early [[tRNA]]-like ribozymes may have had different affinities for amino acids, with codons emerging from another part of the ribozyme that exhibited random variability. Once enough [[peptide]]s were coded for, any major random change in the genetic code would have been lethal; hence it became "frozen".<ref name="Crick_1968" />
*Stereochemical affinity: the genetic code is a result of a high affinity between each amino acid and its codon or anti-codon; the latter option implies that pre-tRNA molecules matched their corresponding amino acids by this affinity. Later during evolution, this matching was gradually replaced with matching by aminoacyl-tRNA synthetases.<ref name="Erives_2011" /><ref name="Hopfield_1978">{{cite journal | vauthors = Hopfield JJ | title = Origin of the genetic code: a testable hypothesis based on tRNA structure, sequence, and kinetic proofreading | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 75 | issue = 9 | pages = 4334–4338 | date = September 1978 | pmid = 279919 | pmc = 336109 | doi = 10.1073/pnas.75.9.4334 | doi-access = free | bibcode = 1978PNAS...75.4334H }}</ref><ref name="Yarus_2009" />
*Optimality: the genetic code continued to evolve after its initial creation, so that the current code maximizes some [[fitness (biology)|fitness]] function, usually some kind of error minimization.<ref name="Erives_2011" /><ref name="Freeland_2000" /><ref>{{cite journal | vauthors = Brown SM, Voráček V, Freeland S | title = What Would an Alien Amino Acid Alphabet Look Like and Why? | journal = Astrobiology | volume = 23 | issue = 5 | pages = 536–549 | date = May 2023 | pmid = 37022727 | doi = 10.1089/ast.2022.0107 | s2cid = 257983174 | bibcode = 2023AsBio..23..536B }}</ref>

Hypotheses have addressed a variety of scenarios:<ref name="Knight_1999">{{cite journal | vauthors = Knight RD, Freeland SJ, Landweber LF | title = Selection, history and chemistry: the three faces of the genetic code | journal = Trends in Biochemical Sciences | volume = 24 | issue = 6 | pages = 241–247 | date = June 1999 | pmid = 10366854 | doi = 10.1016/S0968-0004(99)01392-4 }}</ref>
* Chemical principles govern specific RNA interaction with amino acids. Experiments with [[aptamer]]s showed that some amino acids have a selective chemical affinity for their codons.<ref name="Knight_1998">{{cite journal | vauthors = Knight RD, Landweber LF | title = Rhyme or reason: RNA-arginine interactions and the genetic code | journal = Chemistry & Biology | volume = 5 | issue = 9 | pages = R215–R220 | date = September 1998 | pmid = 9751648 | doi = 10.1016/S1074-5521(98)90001-1 | doi-access = free }}</ref> Experiments showed that of 8 amino acids tested, 6 show some RNA triplet-amino acid association.<ref name="Yarus_2010">{{cite book | vauthors = Yarus M | title = Life from an RNA World: The Ancestor Within | year = 2010 | url = {{google books | plainurl = y | id = -YLBMmJE1WwC}}|publisher=Harvard University Press|isbn=978-0-674-05075-4}}</ref><ref name="Yarus_2009">{{cite journal | vauthors = Yarus M, Widmann JJ, Knight R | title = RNA-amino acid binding: a stereochemical era for the genetic code | journal = Journal of Molecular Evolution | volume = 69 | issue = 5 | pages = 406–429 | date = November 2009 | pmid = 19795157 | doi = 10.1007/s00239-009-9270-1 | doi-access = free | bibcode = 2009JMolE..69..406Y }}</ref>
* Biosynthetic expansion. The genetic code grew from a simpler earlier code through a process of "biosynthetic expansion". Primordial life "discovered" new amino acids (for example, as by-products of [[metabolism]]) and later incorporated some of these into the machinery of genetic coding.<ref name="Pathways of Genetic Code Evolution"/> Although much circumstantial evidence has been found to suggest that fewer amino acid types were used in the past,<ref name="Brooks_2002">{{cite journal | vauthors = Brooks DJ, Fresco JR, Lesk AM, Singh M | title = Evolution of amino acid frequencies in proteins over deep time: inferred order of introduction of amino acids into the genetic code | journal = Molecular Biology and Evolution | volume = 19 | issue = 10 | pages = 1645–1655 | date = October 2002 | pmid = 12270892 | doi = 10.1093/oxfordjournals.molbev.a003988 | doi-access = free }}</ref> precise and detailed hypotheses about which amino acids entered the code in what order are controversial.<ref name="Amirnovin_1997">{{cite journal | vauthors = Amirnovin R | title = An analysis of the metabolic theory of the origin of the genetic code | journal = Journal of Molecular Evolution | volume = 44 | issue = 5 | pages = 473–476 | date = May 1997 | pmid = 9115171 | doi = 10.1007/PL00006170 | s2cid = 23334860 | bibcode = 1997JMolE..44..473A }}</ref><ref name="Ronneberg_2000">{{cite journal | vauthors = Ronneberg TA, Landweber LF, Freeland SJ | title = Testing a biosynthetic theory of the genetic code: fact or artifact? | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 25 | pages = 13690–13695 | date = December 2000 | pmid = 11087835 | pmc = 17637 | doi = 10.1073/pnas.250403097 | doi-access = free | bibcode = 2000PNAS...9713690R }}</ref> However, several studies have suggested that Gly, Ala, Asp, Val, Ser, Pro, Glu, Leu, Thr may belong to a group of early-addition amino acids, whereas Cys, Met, Tyr, Trp, His, Phe may belong to a group of later-addition amino acids.<ref>{{cite journal | vauthors = Trifonov EN | title = The origin of the genetic code and of the earliest oligopeptides | journal = Research in Microbiology | volume = 160 | issue = 7 | pages = 481–486 | date = September 2009 | pmid = 19524038 | doi = 10.1016/j.resmic.2009.05.004 }}</ref><ref>{{cite journal | vauthors = Higgs PG, Pudritz RE | title = A thermodynamic basis for prebiotic amino acid synthesis and the nature of the first genetic code | journal = Astrobiology | volume = 9 | issue = 5 | pages = 483–490 | date = June 2009 | pmid = 19566427 | doi = 10.1089/ast.2008.0280 | arxiv = 0904.0402 | s2cid = 9039622 | bibcode = 2009AsBio...9..483H }}</ref><ref>{{cite journal | vauthors = Chaliotis A, Vlastaridis P, Mossialos D, Ibba M, Becker HD, Stathopoulos C, Amoutzias GD | title = The complex evolutionary history of aminoacyl-tRNA synthetases | journal = Nucleic Acids Research | volume = 45 | issue = 3 | pages = 1059–1068 | date = February 2017 | pmid = 28180287 | pmc = 5388404 | doi = 10.1093/nar/gkw1182 }}</ref><ref>{{cite journal | vauthors = Ntountoumi C, Vlastaridis P, Mossialos D, Stathopoulos C, Iliopoulos I, Promponas V, Oliver SG, Amoutzias GD | title = Low complexity regions in the proteins of prokaryotes perform important functional roles and are highly conserved | journal = Nucleic Acids Research | volume = 47 | issue = 19 | pages = 9998–10009 | date = November 2019 | pmid = 31504783 | pmc = 6821194 | doi = 10.1093/nar/gkz730 }}</ref> An alternative analysis of amino acid usage in the [[Last Universal Common Ancestor]] concluded that the amino acids came in the following order: Val, Gly, Ile, Met, Ala, Thr, His, Glu, Cys, Pro, Lys, Ser, Asp, Leu, Asn, Arg, Phe, Tyr, Gln, Trp.<ref name="Wehbi_2024">{{cite journal | vauthors = Wehbi S, Wheeler A, Morel B, Manepalli N, Minh BQ, Lauretta DS, Masel J | title = Order of amino acid recruitment into the genetic code resolved by last universal common ancestor's protein domains | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 121 | issue = 52 | article-number = e2410311121 | date = December 2024 | pmid = 39665745 | pmc = 11670089 | doi = 10.1073/pnas.2410311121 | bibcode = 2024PNAS..12110311W }}</ref> It was pointed out that the late appearance of sulfur-containing cysteine and methionine was concluded in part from their absence of the sulfur-free [[Miller–Urey experiment]], that early life is believed to have used [[S-adenosyl methionine]], and that while histidine is hard to make abiotically, it is straightforward to synthesize in an organism that already has sophisticated RNA and hence purine synthesis.<ref name="Wehbi_2024" />
* Natural selection has led to codon assignments of the genetic code that minimize the effects of [[mutation]]s.<ref name="Freeland_2003">{{cite journal | vauthors = Freeland SJ, Wu T, Keulmann N | title = The case for an error minimizing standard genetic code | journal = Origins of Life and Evolution of the Biosphere | volume = 33 | issue = 4–5 | pages = 457–477 | date = October 2003 | pmid = 14604186 | doi = 10.1023/A:1025771327614 | s2cid = 18823745 | bibcode = 2003OLEB...33..457F }}</ref> A recent hypothesis<ref name="Baranov_2009">{{cite journal | vauthors = Baranov PV, Venin M, Provan G | title = Codon size reduction as the origin of the triplet genetic code | journal = PLOS ONE | volume = 4 | issue = 5 | article-number = e5708 | date = May 2009 | pmid = 19479032 | pmc = 2682656 | doi = 10.1371/journal.pone.0005708 | veditors = Gemmell NJ | doi-access = free | bibcode = 2009PLoSO...4.5708B }}</ref> suggests that the triplet code was derived from codes that used longer than triplet codons (such as quadruplet codons). Longer than triplet decoding would increase codon redundancy and would be more error resistant. This feature could allow accurate decoding absent complex translational machinery such as the [[ribosome]], such as before cells began making ribosomes.
* Information channels: [[information theory|Information-theoretic]] approaches model the process of translating the genetic code into corresponding amino acids as an error-prone information channel.<ref name="Tlusty_2007">{{cite journal | vauthors = Tlusty T | title = A model for the emergence of the genetic code as a transition in a noisy information channel | journal = Journal of Theoretical Biology | volume = 249 | issue = 2 | pages = 331–342 | date = November 2007 | pmid = 17826800 | doi = 10.1016/j.jtbi.2007.07.029 | arxiv = 1007.4122 | s2cid = 12206140 | bibcode = 2007JThBi.249..331T }}</ref> The inherent noise (that is, the error) in the channel poses the organism with a fundamental question: how can a genetic code be constructed to withstand noise<ref>{{cite book | vauthors = Sonneborn TM | veditors = Bryson V, Vogel H | title = Evolving genes and proteins | location = New York | pages = 377–397 | date = 1965 | publisher = Academic Press }}</ref> while accurately and efficiently translating information? These [[rate-distortion theory|"rate-distortion"]] models<ref name="pmid 18352335">{{cite journal | vauthors = Tlusty T | title = Rate-distortion scenario for the emergence and evolution of noisy molecular codes | journal = Physical Review Letters | volume = 100 | issue = 4 | date = February 2008 | pmid = 18352335 | doi = 10.1103/PhysRevLett.100.048101 | arxiv = 1007.4149 | s2cid = 12246664 | bibcode = 2008PhRvL.100d8101T | article-number = 048101 }}</ref> suggest that the genetic code originated as a result of the interplay of the three conflicting evolutionary forces: the needs for diverse amino acids,<ref name="Sella_2006">{{cite journal | vauthors = Sella G, Ardell DH | title = The coevolution of genes and genetic codes: Crick's frozen accident revisited | journal = Journal of Molecular Evolution | volume = 63 | issue = 3 | pages = 297–313 | date = September 2006 | pmid = 16838217 | doi = 10.1007/s00239-004-0176-7 | s2cid = 1260806 | bibcode = 2006JMolE..63..297S }}</ref> for error-tolerance<ref name="Freeland_2003" /> and for minimal resource cost. The code emerges at a transition when the mapping of codons to amino acids becomes nonrandom. The code's emergence is governed by the [[topology]] defined by the probable errors and is related to the [[map coloring problem]].<ref name="pmid 20558115">{{cite journal | vauthors = Tlusty T | title = A colorful origin for the genetic code: information theory, statistical mechanics and the emergence of molecular codes | journal = Physics of Life Reviews | volume = 7 | issue = 3 | pages = 362–376 | date = September 2010 | pmid = 20558115 | doi = 10.1016/j.plrev.2010.06.002 | arxiv = 1007.3906 | s2cid = 1845965 | bibcode = 2010PhLRv...7..362T }}</ref>
*Game theory: Models based on [[signaling game]]s combine elements of game theory, natural selection and information channels. Such models have been used to suggest that the first polypeptides were likely short and had non-enzymatic function. Game theoretic models suggested that the organization of RNA strings into cells may have been necessary to prevent "deceptive" use of the genetic code, i.e. preventing the ancient equivalent of viruses from overwhelming the RNA world.<ref name="Jee_2013">{{cite journal | vauthors = Jee J, Sundstrom A, Massey SE, Mishra B | title = What can information-asymmetric games tell us about the context of Crick's 'frozen accident'? | journal = Journal of the Royal Society, Interface | volume = 10 | issue = 88 | article-number = 20130614 | date = November 2013 | pmid = 23985735 | pmc = 3785830 | doi = 10.1098/rsif.2013.0614 }}</ref>
*Stop codons: Codons for translational stops are also an interesting aspect to the problem of the origin of the genetic code. As an example for addressing stop codon evolution, it has been suggested that the stop codons are such that they are most likely to terminate translation early in the case of a [[frame shift]] error.<ref>{{cite journal | vauthors = Itzkovitz S, Alon U | title = The genetic code is nearly optimal for allowing additional information within protein-coding sequences | journal = Genome Research | volume = 17 | issue = 4 | pages = 405–412 | date = April 2007 | pmid = 17293451 | pmc = 1832087 | doi = 10.1101/gr.5987307 }}</ref> In contrast, some stereochemical molecular models explain the origin of stop codons as "unassignable".<ref name="Erives_2011" />

== See also ==
* [[List of genetic engineering software]]
* [[Codon tables]]

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin}}
* {{cite book | vauthors = Griffiths AJ, Miller JH, Suzuki DT, Lewontin RC, Gilbert WM | title = An Introduction to genetic analysis | location = San Francisco | date = 1999 | publisher = W.H. Freeman | isbn = 978-0-7167-3771-1 | edition = 7th | url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=iga.TOC | archive-url = https://web.archive.org/web/20011224103037/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=iga.TOC | archive-date = 24 December 2001 }}
* {{cite book | vauthors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P | title = Molecular biology of the cell | location = New York | date = 2002 | publisher = Garland Science | isbn = 978-0-8153-3218-3 | edition = 4th | url = https://www.ncbi.nlm.nih.gov/books/NBK21054/?depth=2 }}
* {{cite book | vauthors = Lodish HF, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell JE | title = Molecular cell biology | location = San Francisco | date = 2000 | publisher = W.H. Freeman | isbn = 978-0-7167-3706-3 | url = https://archive.org/details/molecularcellbi000lodi | url-access = registration | edition = 4th }}
* {{cite journal | vauthors = Caskey CT, Leder P | title = The RNA code: nature's Rosetta Stone | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 16 | pages = 5758–5759 | date = April 2014 | pmid = 24756939 | pmc = 4000803 | doi = 10.1073/pnas.1404819111 | doi-access = free | bibcode = 2014PNAS..111.5758C }}
{{Refend}}

== External links ==
{{Commons category|Genetic code}}
* [https://www.ncbi.nlm.nih.gov/Taxonomy/taxonomyhome.html/index.cgi?chapter=cgencodes The Genetic Codes: Genetic Code Tables]
* The [http://www.kazusa.or.jp/codon/ Codon Usage Database] — Codon frequency tables for many organisms
* [http://history.nih.gov/exhibits/nirenberg/ History of deciphering the genetic code] {{Webarchive|url=https://web.archive.org/web/20071021040426/http://history.nih.gov/exhibits/nirenberg/ |date=21 October 2007 }}
{{Genetics}}
{{MolBioGeneExp}}
{{Proteinogenic amino acids}}
{{Biochemistry topics}}
{{Authority control}}
{{Good article}}

{{DEFAULTSORT:Genetic Code}}
[[Category:Gene expression]]
[[Category:Genetics]]
[[Category:Molecular genetics]]
[[Category:Molecular biology]]
[[Category:Protein biosynthesis]]