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{{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="DutilhJurgelenaite2011"/> 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>
{{cite journal |vauthors=Barrell BG, Bankier AT, Drouin J |date=1979 |title=A different genetic code in human mitochondria |journal=Nature |volume=282 |issue=5735 |pages=189–194 |bibcode=1979Natur.282..189B |doi=10.1038/282189a0 |pmid=226894 |s2cid=4335828}} ([https://www.ncbi.nlm.nih.gov/pubmed/226894])</ref> Many slight variants were discovered thereafter,<ref name="url_The_Genetic_Codes_NCBI"/> including various alternative mitochondrial codes.<ref>{{cite journal | vauthors = Jukes TH, Osawa S | s2cid = 19264964 | title = The genetic code in mitochondria and chloroplasts | journal = Experientia | volume = 46 | issue = 11–12 | pages = 1117–26 | date = Dec 1990 | pmid = 2253709 | doi = 10.1007/BF01936921 }}</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 | pages = 99 | date = 1 January 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 = 1481–6 | 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 | display-authors = 3 | title = Evolution of pathogenicity and sexual reproduction in eight Candida genomes | journal = Nature | volume = 459 | issue = 7247 | pages = 657–62 | date = Jun 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="pmid23638388">{{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 | pages = 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="url_The_Genetic_Codes_NCBI">{{cite web | url = https://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi?mode=c | title = The Genetic Codes | vauthors = Elzanowski A, Ostell J | date = 2008-04-07| 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="pmid27881739">{{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 Biol | volume = 6 | issue = 11 | pages = 160246 | date = 2016 | pmid = 27881739 | doi = 10.1098/rsob.160246 | pmc=5133446}}</ref> This type of recoding is induced by a high-readthrough stop codon context<ref name="pmid25247702">{{cite journal | vauthors = Schueren F, Lingner T, George R, Hofhuis J, Gartner J, Thoms S | title = Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals | journal = eLife | volume = 3 | pages = e03640 | date = 2014 | pmid = 25247702 | doi = 10.7554/eLife.03640 | pmc=4359377 | doi-access = free }}</ref> and it is referred to as ''functional translational readthrough''.<ref name="PMC4973966">{{cite journal|author=F. Schueren und S. Thoms |title=Functional Translational Readthrough: A Systems Biology Perspective |journal=PLOS Genetics |volume=12 |issue=8 |page=e1006196 |date=2016 |pmid=27490485 |pmc=4973966 |doi=10.1371/journal.pgen.1006196 |doi-access=free }}</ref>
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