Genetic code

Start/stop codons

Translation starts with a chain initiation factors are also required to start translation. The most common start codon is AUG, which codes for methionine, so most amino acid chains start with methionine.

The three stop codons have been given names: UAG is amber, UGA is opal (sometimes also called umber), and UAA is ochre. "Amber" was named by discoverers Richard Epstein and Charles Steinberg after their friend Harris Bernstein, whose last name means "amber" in German. The other two stop codons were named 'ochre" and "opal" in order to keep the "color names" theme. Stop codons are also called termination codons and they signal release of the nascent polypeptide from the ribosome due to binding of release factors in the absence of cognate tRNAs with anticodons complementary to these stop signals.^[2]

Degeneracy of the genetic code

The genetic code has redundancy but no ambiguity. For example, although codons GAA and GAG both specify glutamic acid (redundancy), neither of them specifies any other amino acid (no ambiguity). The codons encoding one amino acid may differ in any of their three positions. For example the amino acid serine is specified by UCA, UCG, UCC, UCU, AGU, AGC (difference in the first, second or third position).

A position of a codon is said to be a fourfold degenerate site if any nucleotide at this position specifies the same amino acid. For example, the third position of the glycine codons (GGA, GGG, GGC, GGU) is a fourfold degenerate site, because all nucleotide substitutions at this site are synonymous, i.e. they do not change the amino acid. Only the third positions of some codons may be fourfold degenerate. A position of a codon is said to be a twofold degenerate site if only two of four possible nucleotides at this position specify the same amino acid. For example, the third position of the pyrimidines (C/U), so only transversional substitutions (purine to pyrimidine or pyrimidine to purine) in twofold degenerate sites are nonsynonymous. A position of a codon is said to be a non-degenerate site if any mutation at this position results in amino acid substitution. There is only one possible threefold degenerate site where changing three of the four nucleotides has no effect on the amino acid, while changing the fourth possible nucleotide results in a amino acid substitution. This is the third position of an methionine. In computation this position is often treated as a twofold degenerate site.

There are three amino acids encoded by six different codons: tryptophan, specified by the codon UGG. The degeneracy of the genetic code is what accounts for the existence of silent mutations.

Degeneracy results because a triplet code designates 20 amino acids and a stop codon. Because there are four bases, triplet codons are required to produce at least 21 different codes. For example, if there were two bases per codon, then only 16 amino acids could be coded for (4²=16). Because at least 21 codes are required, then 4³ gives 64 possible codons, meaning that some degeneracy must exist.

These properties of the genetic code make it more fault-tolerant for point mutations. For example, in theory, fourfold degenerate codons can tolerate any point mutation at the third position, although codon usage bias restricts this in practice in many organisms; twofold degenerate codons can tolerate one out of the three possible point 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 twofold degenerate sites adds a further fault-tolerance.

A practical consequence of redundancy is that some errors in the genetic code only cause a silent mutation or an error that would not affect the protein because the hydrophilicity or mutation. Rather it is selected for in malarial regions (in a way similar to thalassemia), as heterozygous people have some resistance to the malarial Plasmodium parasite (heterozygote advantage).

These variable codes for amino acids are allowed because of modified bases in the first base of the anticodon of the tRNA, and the base-pair formed is called a inosine and the Non-Watson-Crick U-G basepair.

Variations to the standard genetic code

While slight variations on the standard code had been predicted earlier,^[3] none were discovered until 1979, when researchers studying human mitochondrial genes discovered they used an alternative code. Many slight variants have been discovered since,^[4] including various alternative mitochondrial codes,^[5] as well as small variants such as Mycoplasma translating the codon UGA as tryptophan. In bacteria and archaea, GUG and UUG are common start codons. However, in rare cases, certain specific proteins may use alternative initiation (start) codons not normally used by that species.^[6]

In certain proteins, non-standard amino acids are substituted for standard stop codons, depending upon associated signal sequences in the messenger RNA: UGA can code for pyrrolysine as discussed in the relevant articles. Selenocysteine is now viewed as the 21st amino acid, and pyrrolysine is viewed as the 22nd. A detailed description of variations in the genetic code can be found at the NCBI web site.

However, all known codes have strong similarities to each other, and the coding mechanism is the same for all organisms: three-base codons, tRNA, and ribosomes, reading the code in the same direction, translating the code three letters at a time into sequences of amino acids.

Theories on the origin of the genetic code

Despite the variations that exist, 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 and meta-analysis of transfer RNA suggest it was established soon after the formation of earth.

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 of the many other 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.

There are three themes running through the many theories that seek to explain the evolution of the genetic code (and hence the origin of these patterns).^[7] One is illustrated by recent mutations.^[12].

References

See also

• Crick, Brenner et al. experiment
• Anticodon
• Protein biosynthesis
• Operon
• Lac operon
• Epigenetic code
• Degenerate bases

Further reading

• Griffiths, Anthony J.F.; Miller, Jeffrey H.; Suzuki, David T.; Lewontin, Richard C.; Gelbart, William M. (1999). Introduction to Genetic Analysis (7th ed.). 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.). New York: Garland Publishing. ISBN 0-8153-3218-1
• Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. (1999). Molecular Cell Biology (4th ed.). New York: W. H. Freeman & Co. ISBN 0-7167-3706-X