Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Rewiring the keyboard: evolvability of the genetic code

Nature Reviews Genetics volume 2, pages 49–58 (2001)Cite this article

Key Points

  • There are many variations in the genetic code, both in nuclear and mitochondrial genomes, but all are relatively recent modifications of the 'canonical' code found in the last common ancestor.

  • The recent evolution of the genetic code relies on changes in components of the translation apparatus. In particular, many changes are due to base modifications that occur after transcription.

  • Three theories have attempted to explain the range of changes to the genetic code:

    1. Codon capture: biased mutations can eliminate certain codons from the genome, which are reassigned by neutral processes (that is, in the absence of selection).

    2. Genome minimization: the code evolves to minimize the number of tRNAs required for translation.

    3. Codon ambiguity: evolution of the genetic code is adaptive and occurs through an intermediate stage in which a codon can be translated into more than one amino acid.

  • We find statistical support for the last two of these theories.

  • Changes in the genetic code that are revealed by future studies will be used to test the specific predictions of each of these theories. Future work will also further clarify the roles of mutation and selection in producing new genetic codes.

Abstract

The genetic code evolved in two distinct phases. First, the 'canonical' code emerged before the last universal ancestor; subsequently, this code diverged in numerous nuclear and organelle lineages. Here, we examine the distribution and causes of these secondary deviations from the canonical genetic code. The majority of non-standard codes arise from alterations in the tRNA, with most occurring by post-transcriptional modifications, such as base modification or RNA editing, rather than by substitutions within tRNA anticodons.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Overview of translation.
Figure 2: Composite phylogeny of variant codes.
Figure 3: The genetic code and its variants.

Similar content being viewed by others

References

  1. Crick, F. H. C. The origin of the genetic code. J. Mol. Biol. 38, 367–379 (1968).Seminal introduction to the origin and evolution of the genetic code, best known for its exposition of the 'frozen accident' theory (that the code became fixed at a suboptimal state, because to change it would be deleterious).

    Article  CAS  PubMed  Google Scholar 

  2. Knight, R. D., Freeland, S. J. & Landweber, L. F. Selection, history and chemistry: the three faces of the genetic code. Trends Biochem. Sci. 24, 241–247 (1999).

    Article  CAS  PubMed  Google Scholar 

  3. Szathmáry, E. The origin of the genetic code: amino acids as cofactors in an RNA world. Trends Genet. 15, 223–229 (1999).

    Article  PubMed  Google Scholar 

  4. Barrell, B. G., Bankier, A. T. & Drouin, J. A different genetic code in human mitochondria. Nature 282, 189–194 ( 1979).

    Article  CAS  PubMed  Google Scholar 

  5. Osawa, S. Evolution of the Genetic Code (Oxford Univ. Press, Oxford, 1995).Exposition of the 'codon capture' hypothesis, which proposes a neutral mechanism for codon reassignment through a stage in which the codon disappears from the genome entirely.

    Google Scholar 

  6. Schultz, D. W. & Yarus, M. On malleability in the genetic code . J. Mol. Evol. 42, 597– 601 (1996).Exposition of the 'ambiguous intermediate' hypothesis, which suggests that the genetic code changes through a state in which some codons have more than one meaning.

    Article  CAS  PubMed  Google Scholar 

  7. Santos, M. A., Cheesman, C., Costa, V., Moradas-Ferreira, P. & Tuite, M. F. Selective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp. Mol. Microbiol. 31, 937–947 (1999).Provides experimental support for the idea that ambiguous decoding can be advantageous in some circumstances.

    Article  CAS  PubMed  Google Scholar 

  8. Wagner, G. P. & Altenberg, L. Complex adaptations and the evolution of evolvability. Evolution 50, 967– 976 (1996).

    Article  PubMed  Google Scholar 

  9. Andersson, S. G. & Kurland, C. G. Genomic evolution drives the evolution of the translation system. Biochem. Cell Biol. 73, 775–787 ( 1995).Most complete exposition of the 'genome reduction' hypothesis, which suggests that pressure to minimize mitochondrial genomes leads to the reassignment of specific codons.

    Article  CAS  PubMed  Google Scholar 

  10. Sugita, T. & Nakase, T. Non-universal usage of the leucine CUG codon and the molecular phylogeny of the genus Candida. Syst. Appl. Microbiol. 22, 79–86 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Tourancheau, A. B., Tsao, N., Klobutcher, L. A., Pearlman, R. E. & Adoutte, A. Genetic code deviations in the ciliates: evidence for multiple and independent events. EMBO J. 14, 3262–3267 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ehara, M., Inagaki, Y., Watanabe, K. I. & Ohama, T. Phylogenetic analysis of diatom coxI genes and implications of a fluctuating GC content on mitochondrial genetic code evolution. Curr. Genet. 37, 29–33 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  13. Hayashi-Ishimaru, Y., Ohama, T., Kawatsu, Y., Nakamura, K. & Osawa, S. UAG is a sense codon in several chlorophycean mitochondria . Curr. Genet. 30, 29–33 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Hayashi-Ishimaru, Y., Ehara, M., Inagaki, Y. & Ohama, T. A deviant mitochondrial genetic code in prymnesiophytes (yellow-algae): UGA codon for tryptophan. Curr. Genet. 32, 296–299 (1997).

    Article  CAS  PubMed  Google Scholar 

  15. Castresana, J., Feldmaier-Fuchs, G. & Pääbo, S. Codon reassignment and amino acid composition in hemichordate mitochondria. Proc. Natl Acad. Sci. USA 95, 3703–3707 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Osawa, S., Jukes, T. H., Watanabe, K. & Muto, A. Recent evidence for evolution of the genetic code. Microbiol. Rev. 56, 229–264 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Lagerkvist, U. Unorthodox codon reading and the evolution of the genetic code. Cell 23, 305–306 ( 1981).

    Article  CAS  PubMed  Google Scholar 

  18. Knight, R. D. & Landweber, L. F. Guilt by association: the arginine case revisited. RNA 6, 499– 510 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ito, K., Uno, M. & Nakamura, Y. A tripeptide 'anticodon' deciphers stop codons in messenger RNA. Nature 403, 680–684 (2000).Experimental demonstration that bacterial release factors use only a few amino acids to recognize the specific mRNA stop codons.

    Article  CAS  PubMed  Google Scholar 

  20. Perret, V. et al. Relaxation of a transfer RNA specificity by removal of modified nucleotides. Nature 344, 787– 789 (1990).

    Article  CAS  PubMed  Google Scholar 

  21. Muramatsu, T. et al. Codon and amino-acid specificities of a transfer RNA are both converted by a single post-transcriptional modification. Nature 336, 179–181 ( 1988).

    Article  CAS  PubMed  Google Scholar 

  22. Cermakian, N. & Cedegren, R. C. in Modification and Editing of RNA (eds Grosjean, H. & Benne, R.) 535– 541 (American Society for Microbiology, Washington, 1998).Reviews the distribution of modified bases throughout the three domains of life, and argues that many of the modifications pre-date the last common ancestor of extant life.

    Book  Google Scholar 

  23. Unrau, P. J. & Bartel, D. P. RNA-catalysed nucleotide synthesis . Nature 395, 260–263 (1998).

    Article  CAS  PubMed  Google Scholar 

  24. Levy, M. & Miller, S. L. The prebiotic synthesis of modified purines and their potential role in the RNA world. J. Mol. Evol. 48, 631–637 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  25. Edmonds, C. G. et al. Posttranscriptional modification of tRNA in thermophilic archaea (Archaebacteria). J. Bacteriol. 173, 3138 –3148 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Giege, R., Sissler, M. & Florentz, C. Universal rules and idiosyncratic features in tRNA identity . Nucleic Acids Res. 26, 5017– 5035 (1998).Excellent review of tRNA identity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Murgola, E. J. tRNA, suppression, and the code. Annu. Rev. Genet. 19, 57–80 (1985).

    Article  CAS  PubMed  Google Scholar 

  28. Arnez, J. G. & Moras, D. Structural and functional considerations of the aminoacylation reaction. Trends Biochem. Sci. 22, 211–216 (1997).

    Article  CAS  PubMed  Google Scholar 

  29. Matsuyama, S., Ueda, T., Crain, P. F., McCloskey, J. A. & Watanabe, K. A novel wobble rule found in starfish mitochondria. Presence of 7-methylguanosine at the anticodon wobble position expands decoding capability of tRNA. J. Biol. Chem. 273, 3363–3368 (1998). This is one of a series of papers from Watanabe's lab, and shows the role of specific base modifications in changing the genetic code in mitochondria.

    Article  CAS  PubMed  Google Scholar 

  30. Tomita, K., Ueda, T. & Watanabe, K. 7-Methylguanosine at the anticodon wobble position of squid mitochondrial tRNA(Ser)GCU: molecular basis for assignment of AGA/AGG codons as serine in invertebrate mitochondria. Biochim. Biophys. Acta 1399, 78–82 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  31. Alfonzo, J. D., Blanc, V., Estevez, A. M., Rubio, M. A. & Simpson, L. C to U editing of the anticodon of imported mitochondrial tRNA(Trp) allows decoding of the UGA stop codon in Leishmania tarentolae. EMBO J. 18, 7056–7062 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Small, I., Wintz, H., Akashi, K. & Mireau, H. Two birds with one stone: genes that encode products targeted to two or more compartments . Plant Mol. Biol. 38, 265– 277 (1998).

    Article  CAS  PubMed  Google Scholar 

  33. Mazauric, M. H., Roy, H. & Kern, D. tRNA glycylation system from Thermus thermophilus. tRNAGly identity and functional interrelation with the glycylation systems from other phylae. Biochemistry 38, 13094– 13105 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. Crick, F. H. C. The recent excitement in the coding problem. Prog. Nucleic Acids 1, 163–217 ( 1963).

    CAS  Google Scholar 

  35. Crick, F. H. Codon–anticodon pairing: the wobble hypothesis. J. Mol. Biol. 19, 548–555 ( 1966).

    Article  CAS  PubMed  Google Scholar 

  36. Osawa, S. & Jukes, T. H. Codon reassignment (codon capture) in evolution. J. Mol. Evol. 28, 271– 278 (1989).

    Article  CAS  PubMed  Google Scholar 

  37. Schultz, D. W. & Yarus, M. Transfer RNA mutation and the malleability of the genetic code. J. Mol. Biol. 235, 1377–1380 (1994).

    Article  CAS  PubMed  Google Scholar 

  38. Andersson, S. G. & Kurland, C. G. Reductive evolution of resident genomes. Trends Microbiol. 6, 263–268 (1998).

    Article  CAS  PubMed  Google Scholar 

  39. Takai, K., Takaku, H. & Yokoyama, S. In vitro codon-reading specificities of unmodified tRNA molecules with different anticodons on the sequence background of Escherichia coli tRNASer. Biochem. Biophys. Res. Commun. 257, 662–667 (1999).

    Article  CAS  PubMed  Google Scholar 

  40. Szathmáry, E. Codon swapping as a possible evolutionary mechanism. J. Mol. Evol. 32, 178–182 ( 1991).

    Article  Google Scholar 

  41. Lagerkvist, U. 'Two out of three': An alternative method for codon reading. Proc. Natl Acad. Sci. USA 75, 1759–1762 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Saks, M. E., Sampson, J. R. & Abelson, J. Evolution of a transfer RNA gene through a point mutation in the anticodon. Science 279, 1665– 1670 (1998).Demonstration that a single-base change at the anticodon of a tRNA can change both its decoding and aminoacylation specificities. This paper has important implications for the use of tRNA phylogeny to track the evolution of the genetic code.

    Article  CAS  PubMed  Google Scholar 

  43. Pallanck, K., Pak, M. & Schulman, L. H. in tRNA: Structure, Biosynthesis, and Function (eds Söll, D. & RajBhandary, U.) 371–394 (American Society for Microbiology, Washington, 1995).

    Book  Google Scholar 

  44. Murgola, E. J. in tRNA: Structure, Biosynthesis and Function (eds Söll, D. & RajBhandary, U.) 491–509 (American Society for Microbiology, Washington, 1995).

    Book  Google Scholar 

  45. Jukes, T. H. Genetic code 1990. Outlook. Experientia 46, 1149–1157 (1990).

    Article  CAS  PubMed  Google Scholar 

  46. Tomita, K. et al. Codon reading patterns in Drosophila melanogaster mitochondria based on their tRNA sequences: a unique wobble rule in animal mitochondria . Nucleic Acids Res. 27, 4291– 4297 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Schimmel, P., Giege, R., Moras, D. & Yokoyama, S. An operational genetic code for amino acids and possible relationship to genetic code. Proc. Natl Acad. Sci. USA 90, 8763– 8768 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wright, E. V. Gadsby: a story of over 50,000 words without using the letter 'E' (Wetzel, Los Angeles, 1939).

    Google Scholar 

  49. Jukes, T. H. Neutral changes and modifications of the genetic code. Theor. Popul. Biol. 49, 143–145 ( 1996).

    Article  CAS  PubMed  Google Scholar 

  50. Keeling, P. J. & Doolittle, W. F. Widespread and ancient distribution of a noncanonical genetic Code in diplomonads. Mol. Biol. Evol. 14, 895–901 (1997).

    Article  CAS  PubMed  Google Scholar 

  51. Freeland, S. J. & Hurst, L. D. The genetic code is one in a million. J. Mol. Evol. 47, 238 –248 (1998).A statistical argument to show that the actual genetic code minimizes the effects of error far better than would be expected by chance.

    Article  CAS  PubMed  Google Scholar 

  52. Freeland, S. J., Knight, R. D., Landweber, L. F. & Hurst, L. D. Early fixation of an optimal genetic code. Mol. Biol. Evol. 17, 511–518 (2000).

    Article  CAS  PubMed  Google Scholar 

  53. Yarus, M. & Schultz, D. W. Response: Further comments on codon reassignment. J. Mol. Evol. 45, 1– 8 (1997).

    Article  Google Scholar 

  54. Curran, J. F. Decoding with the A:I wobble pair is inefficient. Nucleic Acids Res. 23, 683–688 ( 1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Andersson, G. E. & Kurland, C. G. An extreme codon preference strategy: codon reassignment. Mol. Biol. Evol. 8, 530–544 ( 1991).

    CAS  PubMed  Google Scholar 

  56. Yarus, M. RNA-ligand chemistry: a testable source for the genetic code. RNA 6, 475–484 ( 2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Schneider, S. U. & de Groot, E. J. Sequences of two rbcS cDNA clones of Batophora oerstedii: structural and evolutionary considerations. Curr. Genet. 20, 173– 175 (1991).

    Article  CAS  PubMed  Google Scholar 

  58. Lozupone, C. A., Knight, R. D. & Landweber, L. F. The molecular basis of nuclear genetic code change in ciliates. Curr. Biol. (in the press).

  59. Oba, T., Andachi, Y., Muto, A. & Osawa, S. CGG: an unassigned or nonsense codon in Mycoplasma capricolum. Proc. Natl Acad. Sci. USA 88, 921–925 ( 1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kuck, U., Jekosch, K. & Holzamer, P. DNA sequence analysis of the complete mitochondrial genome of the green alga Scenedesmus obliquus: evidence for UAG being a leucine and UCA being a non-sense codon. Gene 253 , 13–18 (2000).

    Article  CAS  PubMed  Google Scholar 

  61. Kano, A., Ohama, T., Abe, R. & Osawa, S. Unassigned or nonsense codons in Micrococcus luteus. J. Mol. Biol. 230, 51–56 (1993).

    Article  CAS  PubMed  Google Scholar 

  62. Cavalier-Smith, T. Kingdom protozoa and its 18 phyla. Microbiol. Rev. 57, 953–994 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Telford, M. J., Herniou, E. A., Russell, R. B. & Littlewood, D. T. Changes in mitochondrial genetic codes as phylogenetic characters: two examples from the flatworms. Proc. Natl Acad. Sci. USA 97, 11359–11364 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Inagaki, Y., Ehara, M., Watanabe, K. I., Hayashi-Ishimaru, Y. & Ohama, T. Directionally evolving genetic code: the UGA codon from stop to tryptophan in mitochondria. J. Mol. Evol. 47, 378–384 (1998).

    Article  CAS  PubMed  Google Scholar 

  65. Clark-Walker, G. D. & Weiller, G. F. The structure of the small mitochondrial DNA of Kluyveromyces thermotolerans is likely to reflect the ancestral gene order in fungi. J. Mol. Evol. 38, 593–601 (1994).

    Article  CAS  PubMed  Google Scholar 

  66. Laforest, M. J., Roewer, I. & Lang, B. F. Mitochondrial tRNAs in the lower fungus Spizellomyces punctatus: tRNA editing and UAG 'stop' codons recognized as leucine. Nucleic Acids Res. 25, 626–632 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Wilson, R. J. & Williamson, D. H. Extrachromosomal DNA in the Apicomplexa. Microbiol. Mol. Biol. Rev. 61, 1–16 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Yasuhira, S. & Simpson, L. Phylogenetic affinity of mitochondria of Euglena gracilis and kinetoplastids using cytochrome oxidase I and hsp60. J. Mol. Evol. 44, 341– 347 (1997).

    Article  CAS  PubMed  Google Scholar 

  69. Lovett, P. S. et al. UGA can be decoded as tryptophan at low efficiency in Bacillus subtilis. J. Bacteriol. 173, 1810–1812 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Tomita, K., Ueda, T. & Watanabe, K. The presence of pseudouridine in the anticodon alters the genetic code: a possible mechanism for assignment of the AAA lysine codon as asparagine in echinoderm mitochondria. Nucleic Acids Res. 27, 1683–1689 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Horie, N. et al. Modified nucleosides in the first positions of the anticodons of tRNA(Leu)4 and tRNA(Leu)5 from Escherichia coli. Biochemistry 38, 207–217 ( 1999).

    Article  CAS  PubMed  Google Scholar 

  72. Tomita, K., Ueda, T. & Watanabe, K. 5-formylcytidine (f5C) found at the wobble position of the anticodon of squid mitochondrial tRNA(Met)CAU. Nucleic Acids Symp. Ser. 37, 197–198 ( 1997).

    CAS  Google Scholar 

  73. Watanabe, Y. et al. Primary sequence of mitochondrial tRNA(Arg) of a nematode Ascaris suum: occurrence of unmodified adenosine at the first position of the anticodon. Biochim. Biophys. Acta 1350, 119–122 (1997).

    Article  CAS  PubMed  Google Scholar 

  74. Boren, T. et al. Undiscriminating codon reading with adenosine in the wobble position . J. Mol. Biol. 230, 739– 749 (1993).

    Article  CAS  PubMed  Google Scholar 

  75. Grimm, M., Brunen-Nieweler, C., Junker, V., Heckmann, K. & Beier, H. The hypotrichous ciliate Euplotes octocarinatus has only one type of tRNACys with GCA anticodon encoded on a single macronuclear DNA molecule. Nucleic Acids Res. 26, 4557–4565 ( 1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Watanabe, K. & Osawa, S. in tRNA: Structure, Biosynthesis, and Function (eds Söll, D. & RajBhandary, U.) 225– 250 (American Society for Microbiology, Washington, 1995).

    Book  Google Scholar 

  77. Yokoyama, S. & Nishimura, S. in tRNA: Structure, Biosynthesis, and Function (eds. Söll, D. & RajBhandary, U.) 207– 223 (American Society for Microbiology, Washington 1995).

    Book  Google Scholar 

  78. Björk, G. R. in Modification and Editing of RNA (eds Grosjean, H. & Benne, R.) 577–581 (American Society for Microbiology, Washington, 1998).

    Google Scholar 

  79. Curran, J. F. in Modification and Editing of RNA (eds Grosjean, H. & Benne, R.) 493–516 (American Society for Microbiology, Washington, 1998).Excellent review of the base-pairing roles of normal and modified bases at the wobble position in the tRNA anticodon.

    Book  Google Scholar 

  80. Motorin, Y. & Grosjean, H. in Modification and Editing of RNA (eds Grosjean, H. & Benne, R.) 543–549 (American Society for Microbiology, Washington, 1998 ).

    Google Scholar 

Download references

Acknowledgements

S.J.F. is supported by a Human Frontier Science Program fellowship.

Author information

Authors and Affiliations

  1. Department of Ecology and Evolutionary Biology, Princeton University, Princeton, 08544, New Jersey, USA

    Robin D. Knight, Stephen J. Freeland & Laura F. Landweber

Authors
  1. Robin D. Knight
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen J. Freeland
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laura F. Landweber
    View author publications

    You can also search for this author in PubMed Google Scholar

Supplementary information

Related links

Related links

FURTHER INFORMATION

The Tree of Life

The RNA world web site

Laura Landweber's lab page

RNA editing

ENCYCLOPEDIA OF LIFE SCIENCES

Transfer RNA

RNA editing

Genetic code and its variants

tRNA modification

Glossary

DIPLOMONADS

Among the earliest-diverging eukaryotes, these unicellular organisms have two nuclei, but lack mitochondria. The gastrointestinal parasite Giardia is a diplomonad.

RELEASE FACTORS

Proteins involved in translation termination that specifically recognize stop codons and catalyse the disassembly of the translation complex.

AMINOACYL-tRNA SYNTHETASE

The enzyme that attaches an amino acid to its cognate tRNA(s).

WOBBLE RULES

An extension to Watson–Crick base pairing, these rules indicate that, in the context of the first anticodon position of the tRNA (complementary to the third codon position), more flexibility allows non-standard base pairs (such as G with U rather than with C).

RIBOZYME

RNA that can perform a catalytic task, such as the self-splicing Group I intron in the ciliate Tetrahymena.

THIOL

A thiol (or sulphydryl) group is a chemical group that contains sulphur and hydrogen.

SUPPRESSOR MUTATION

A mutation that counteracts the effects of another mutation. A suppressor mutation maps at a different site to that of the mutation that it counteracts, either within the gene or at a more distant locus. Mutations in tRNAs often act as suppressors, because they can change the meaning of the mutated codon back to the original (albeit usually at a low level, because efficient suppressors are often lethal).

RNA EDITING

Changes in the RNA sequence after transcription is completed. Examples include modification of C to U or of A to I by deamination, or insertion and/or deletion of particular bases.

FAMILY BOX

A set of four codons that are identical at the first two positions, differ only at the third position and code for the same amino acid. For instance, GUU, GUC, GUA and GUG comprise a family box for valine in all known codes.

BINOMIAL TEST

If an observation has only two possible outcomes and there are multiple observations, the binomial distribution gives the probability that x or more outcomes of a given type would occur by chance.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Knight, R., Freeland, S. & Landweber, L. Rewiring the keyboard: evolvability of the genetic code. Nat Rev Genet 2, 49–58 (2001). https://doi.org/10.1038/35047500

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35047500

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing