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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 = <i>Escherichia coli</i> with a 57-codon genetic code | journal = Science | article-number = eady4368 | date = July 2025 | pmid = 40743368 | doi = 10.1126/science.ady4368 | biorxiv = 10.1101/2025.05.02.651837 | doi-access = free }}</ref>
==Features==
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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 =
===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 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 |
[[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>{{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><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 | pages = 608 | date = 10 January 2013 | url = {{google books | plainurl = y | id = 5jhH0HTjEdkC}}|publisher=OUP USA|isbn=978-0-19-976644-4}}</ref>
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* 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>{{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> 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 | pages = e5708 | date = May 2009 | pmid = 19479032 | pmc = 2682656 | doi = 10.1371/journal.pone.0005708 |
* 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 | pages = 048101 | 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 | pages = 20130614 | date = November 2013 | pmid = 23985735 | pmc = 3785830 | doi = 10.1098/rsif.2013.0614 }}</ref>
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