The genetic code is a set of rules, which maps DNA sequences to proteins in the living cell, and is employed in the process of protein synthesis. Nearly all living things use the same genetic code, called the standard genetic code, although a few organisms use minor variations of the standard code.
The genetic information carried by an organism - its genome - is inscribed in a DNA molecule. Each functional portion of this molecule is referred to as a gene. Each gene is transcribed into a short template molecule of the related polymer RNA, which is better suited for protein synthesis. This in turn is translated, by mediation of a machinery consisting of ribosomes and a set of transfer RNAs and associated enzymes, into an amino acid chain (polypeptide), which will then be folded into a protein.
The gene sequence inscribed in DNA, and thus in RNA, is composed of units called codons, each coding for a single amino acid. Both DNA and RNA are comprised of 4 nucleotide bases. In the case of DNA this is comprised of adenine (A), guanine (G), cytosine (C) and thymine (T). RNA is identical with the exception that thymine (T) is substituted with uracil (U). Codons are non-overlapping groups of the three bases. There are 43 = 64 codons. For example, the RNA sequence UUUAAACCC contains the codons UUU, AAA and CCC, each of which specifies one amino acid. So, this RNA sequence represents a protein sequence, three amino acids long. (DNA is also a sequence of nucleotide bases, but there thymine takes the place of uracil.)
The standard genetic code is shown in the following tables. Table 1 shows what amino acid each of the 64 codons specifies. Table 2 shows what codons specify each of the 20 standard amino acids involved in translation. These are called forward and reverse codon tables, respectively. For example, the codon AAU represents the amino acid asparagine (Asp), and cysteine (Cys) is represented by UGU and by UGC.
Table 1: Codon table
1The codon AUG both codes for methionine and serves as an initiation site: the first AUG in an mRNA's coding region is where translation into protein begins.
2This is a start codon for prokaryotes only.
Table 2: Reverse codon table
This table shows the 20 amino acids used in proteins, and the codons that code for each amino acid.
|Ala ||A ||GCU, GCC, GCA, GCG ||Leu ||L ||UUA, UUG, CUU, CUC, CUA, CUG |
|Arg ||R ||CGU, CGC, CGA, CGG, AGA, AGG ||Lys ||K ||AAA, AAG |
|Asn ||N ||AAU, AAC ||Met ||M ||AUG |
|Asp ||D ||GAU, GAC ||Phe ||F ||UUU, UUC |
|Cys ||C ||UGU, UGC ||Pro ||P ||CCU, CCC, CCA, CCG |
|Gln ||Q ||CAA, CAG ||Ser ||S ||UCU, UCC, UCA, UCG, AGU,AGC |
|Glu ||E ||GAA, GAG ||Thr ||T ||ACU, ACC, ACA, ACG |
|Gly ||G ||GGU, GGC, GGA, GGG ||Trp ||W ||UGG |
|His ||H ||CAU, CAC ||Tyr ||Y ||UAU, UAC |
|Ile ||I ||AUU, AUC, AUA ||Val ||V ||GUU, GUC, GUA, GUG |
|Start || ||AUG, GUG ||Stop || ||UAG, UGA, UAA |
Marshall W. Nirenberg and his lab at the National Institutes of Health performed the experiments which first elucidated the correspondence between the codons and the amino acids for which they code. Har Gobind Khorana expanded on Nirenberg's work and found the codes for the amino acids that Nirenberg's methods could not. Khorana and Nirenberg won a share of the 1968 Nobel Prize in Physiology or Medicine for this work.
In classical genetics, the stop codons were given names: UAG was amber, UGA was opal, and UAA was ocher. These names were originally the names of the specific genes in which mutation of each of these stop codons was first detected. Translation starts with a chain initiation codon (start codon). But unlike stop codons, these are not sufficient to begin the process; nearby initiation sequences are also required to induce transcription into mRNA and binding by ribosomes. The most notable start codon is AUG, which also codes for methionine. CUG and UUG, and in prokaryotes GUG and AUU, also work.
Degeneracy of the Genetic Code
Many codons are degenerate, meaning that two or more codons may code for the same amino acid. Degenerate codons typically differ in their third positions; e.g. both GAA and GAG code for the amino acid glutamine. A codon is said to be four_fold degenerate if any nucleotide at its third position specifies the same amino acid; it is said to be two_fold degenerate if only two of four possible nucleotides at its third position specify the same amino acid. In two_fold degenerate codons, the equivalent third position nucleotides are always either two purines (A/G) or two pyrimidines (C/T). The degeneracy of the genetic code is what accounts for the existance of silent mutations.
These properties of the genetic code make it more fault_tolerant for mutations. For example, four_fold degenerate codons can tolerate any mutation at the third position; two_fold degenerate codons can tolerate one out of the three possible mutations at the third position. Since transition mutations (purine to purine or pyrimidine to pyrimidine mutations) are more likely than transversion (purine to pyrimidine or vice_versa) mutations, the equivalence of purines or that of pyrimidines at two_fold degenerate sites adds a further fault_tolerance.
These variable codes for amino acids are possible because of modified bases in the first base of the anticodon, and the basepair formed is called a wobble base pair. The modified bases include inosine and the U-G basepair.
Only two amino acids are specified by a single codon; one of these is the amino-acid methionine, specified by the codon AUG, which also specifies the start of transcription; the other is tryptophan, specified by the codon UGG.
Phase or Reading Frame of a Sequence
Note that a "codon" is entirely defined by your starting position. For example, the string GGGAAACCC, if read from the first position, contains the codons GGG, AAA and CCC. If read from the second position, it contains the codons GGA and AAC (partial codons being ignored). If read starting from the third position, GAA and ACC. Every DNA sequence can thus be read in three reading frames, each of which will produce a radically different amino acid sequence (in our example, Gly-Lys-Pro, Gly-Asp, and Glu-Thr, respectively). The actual frame a protein sequence is translated in is defined by a start codon, usually the first occurence of AUG in the RNA sequence. Mutations that disrupt the reading frame (i.e. insertions or deletions of one or two nucleotide bases) severely impair the function of a protein and are thus exceedingly rare in protein-coding sequences, since they do not often survive purifying selection.
Origin of the genetic code
Numerous variations of the standard genetic code are found in mitochondria, energy_burning organelles. Ciliate protozoa also have some variation in the genetic code: UAG and often UAA code for Glutamine (a variant also found in some green algae), or UGA codes for Cysteine. Another variant is found in some species of the yeast candida, where CUG codes for Serine. In some species of bacteria and archaea, a few non-standard amino acids are substituted for standard stop codons; UGA can code for selenocysteine and UAG can code for pyrrolysine. There may be other non-standard amino acids and codon interpretations that are not known.
Despite these variations, the genetic codes used by all known forms of life on Earth are very similar. Since there are many possible genetic codes that are thought to have similar utility to the one used by Earth life, the theory of evolution suggests that the genetic code was established very early in the history of life.
One can ask the question: is the genetic code completely random, just one set of codon-amino acid correspondences that happened to establish itself and be "frozen in" early in evolution, although functionally any other of the near-infinite set of possible transcription tables would have done just as well? Already a cursory look at the table shows patterns that suggest that this is not the case.
Recent aptamer experiments have shown, that amino acids have indeed a selective chemical affinity for the base triplets that code for them1. This suggests, that the current, complex transcription mechanism involving tRNA and associated enzymes is a later development, and that originally, protein sequences were directly templated on base sequences. Also, evidence has been found that originally the number of different amino acids used may have been considerably smaller than today2.
There are several books available online that go into great detail on this topic. They are available through the NCBI Bookshelf (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books), maintained by the United States National Institutes of Health. In particular the following books would be useful to consult:
- Griffiths, Anthony J.F.; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. (1999). Introduction to Genetic Analysis (7th ed.) (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=iga.TOC). New York: W. H. Freeman & Co. ISBN 0-7167-3771-X
- Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. (2002). Molecular Biology of the Cell (4th ed.) (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=mboc4.TOC&depth=2). New York: Garland Publishing. ISBN 0815332181
- Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. (1999). Molecular Cell Biology (4th ed.) (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=mcb.TOC). New York: W. H. Freeman & Co. ISBN 0-7167-3706-X
Following are references cited in the text of the article.
Note 1: Brooks, Dawn J.; Fresco, Jacques R.; Lesk, Arthur M.; and Singh, Mona. (2002). Evolution of Amino Acid Frequencies in Proteins Over Deep Time: Inferred Order of Introduction of Amino Acids into the Genetic Code (http://mbe.oupjournals.org/cgi/content/full/19/10/1645). Molecular Biology and Evolution 19, 1645-1655.
Note 2: Knight, R.D. and Landweber, L.F. (1998). Rhyme or reason: RNA-arginine interactions and the genetic code. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9751648) Chemistry & Biology 5(9), R215-R220. PDF version of manuscript (http://bayes.colorado.edu/Papers/chmbio98.pdf)