The Genetic Code

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• Four different nucleotides taken three at a time can result in 64 different possible triplet codes; more than enough to encode 20 amino acids. The way that these 64 codes are mapped onto 20 amino acids is first, that one amino acid may be encoded by 1 to 6 different triplet codes, and second, that 3 of the 64 codes, called stop (or termination) codons, specify "end of peptide sequence". Where multiple codons specify the same amino acid, the different codons are used with unequal frequency and this distribution of frequency is referred to as "codon usage". Codon usage varies between species.
• The fact that DNA nucleotides need to be read three at a time to specify a protein sequence implies that a DNA sequence has three different reading frames determined by whether you start at nucleotide one, two, or three. (Nucleotide four will be in the same frame as nucleotide one and so on). Both strands of DNA can be copied into RNA (for translation into protein). Thus, a DNA sequence with its (inferred) complementary strand can specify six different reading frames.

The Genetic Code

The relationship between the codons of nucleic acids, and the amino acids for which they code, is embodied in the Genetic Code, (which is NOT universal since slight variations on it are found in protists, in mitochondria and in chloroplasts). The 64 possible triplets of bases in a codon, and the amino acid coded for are shown in this table :

First               Second Position             Third 
Position   ------------------------------------ Position
  |            U(T)    C       A       G         |
  
  U(T)        Phe     Ser     Tyr     Cys        U(T)
              Phe     Ser     Tyr     Cys        C
              Leu     Ser     STOP    STOP       A
              Leu     Ser     STOP    Trp        G

  C           Leu     Pro     His     Arg        U(T)
              Leu     Pro     His     Arg        C
              Leu     Pro     Gln     Arg        A
              Leu     Pro     Gln     Arg        G

  A           Ile     Thr     Asn     Ser        U(T)
              Ile     Thr     Asn     Ser        C
              Ile     Thr     Lys     Arg        A
              Met     Thr     Lys     Arg        G

  G           Val     Ala     Asp     Gly        U(T)
              Val     Ala     Asp     Gly        C
              Val     Ala     Glu     Gly        A
              Val     Ala     Glu     Gly        G

Some characteristics of the genetic code:

• The genetic code is unambiguous: each codon specifies one amino acid only
• The code is degenerate. One amino acid may be specified by more than one codon. For instance serine is encoded by six codons, glycine by four and lysine by two.
• Note that in most cases sufficient coding is performed by the first two bases, the third (or wobble) base playing a minor role. For instance the four codons that specify glycine (GGU, GGC, GGA and GGG) all start with GG.
• Codons with a similar sequence specify amino acids with similar chemical properties. The codons that specify threonine differ from those specifying serine by their 5' nucleotide. The codons for aspartate and glutamate differ only by their 3' position. Codons with in the middle a pyrimidine generally specify for a hydrophobic amino acid. Thus mutation of the 5' or 3' positions of these codons lead to a substitution of chemically similar amino acids.
• Note also the STOP codons, which cause termination of translation by the ribosome.
• The codon AUG for methionine is also used as start codon.

NB. Different organisms exhibit different statistical preferences of triplet codon usage, as well as using the amino acids in widely varying proportions. See Of URFs and ORFs' by Russell Doolittle, University Science Books (1986) ISBN 0-935702-54-7. Click here to see the codon usage table for the filarial parasite Brugia malayi

The Mitochondrial Genetic Code

Human mitochondrial DNA encodes only 22 tRNA species and these are the only tRNAs used for the translation of mitochondrial mRNAs. This is accomplished by an extreme form of wobble in which U of the anticodon in tRNA can pair with any of the four bases in the third codon position of the mRNA, allowing four codons to be recognized by a single tRNA. In addition some codons specify different amino acids in mitochondria than in the universal code.

Differences between the Universal and Mitochondrial Genetic Codes

Codon	Universal code	Human mitochondrial code
UGA	Stop	Trp
AGA	Arg	Stop
AGG	Arg	Stop
AUA	Ile	Met

Tables with codon usage (Table 10, p 95 Li and Grauer)
Acknowledgment: Modified from: Li and Graur, 1991, Fundamentals of Molecular Evolution , Sinauer Publ.

Last updated: 8 August 1997.