Genetic code

Genetic code

Genetic code, the sequence of nucleotides in deoxyribonucleic acid (DNA) and ribonucleic acid(RNA) that determines the amino acid sequence of proteins. Though the linear sequence of nucleotides in DNA contains the information for protein sequences, proteins are not made directly from DNA. Instead, a messenger RNA (mRNA) molecule is synthesized from the DNA and directs the formation of the protein. RNA is composed of four nucleotides: adenine (A), guanine (G), cytosine (C), and uracil (U). Three adjacent nucleotides constitute a unit known as the codon, which codes for an amino acid. For example, the sequence AUG is a codon that specifies the amino acid methionine. There are 64 possible codons, three of which do not code for amino acids but indicate the end of a protein. The remaining 61 codons specify the 20 amino acids that make up proteins. The AUG codon, in addition to coding for methionine, is found at the beginning of every mRNA and indicates the start of a protein. Because most of the 20 amino acids are coded for by more than one codon, the code is called degenerate.

The genetic code consists of 64 triplets of nucleotides. These triplets are called codons.With three exceptions, each codon encodes for one of the 20 amino acids used in the synthesis of proteins. That produces some redundancy in the code: most of the amino acids being encoded by more than one codon.

One codon, AUG serves two related functions:

  • it signals the start of translation
  • it codes for the incorporation of the amino acid methionine (Met) into the growing polypeptide chain

The genetic code can be expressed as either RNA codons or DNA codons. RNA codons occur in messenger RNA (mRNA) and are the codons that are actually “read” during the synthesis of polypeptides (the process called translation). But each mRNA molecule acquires its sequence of nucleotides by transcription from the corresponding gene. Because DNA sequencing has become so rapid and because most genes are now being discovered at the level of DNA before they are discovered as mRNA or as a protein product, it is extremely useful to have a table of codons expressed as DNA. So here are both.

Note that for each table, the left-hand column gives the first nucleotide of the codon, the 4 middle columns give the second nucleotide, and the last column gives the third nucleotide

The RNA Codons

Genetic code

The DNA Codons

Genetic code

These are the codons as they are read on the sense (5′ to 3′) strand of DNA. Except that the nucleotide thymidine (T) is found in place of uridine (U), they read the same as RNA codons. However, mRNA is actually synthesized using the antisense strand of DNA (3′ to 5′) as the template.

This table could well be called the Rosetta Stone of life.

The Genetic Code (DNA)

Codon Bias

All but two of the amino acids (Met and Trp) can be encoded by from 2 to 6 different codons. However, the genome of most organisms reveals that certain codons are preferred over others. In humans, for example, alanine is encoded by GCC four times as often as by GCG. This probably reflects a greater translation efficiency by the translation apparatus (e.g., ribosomes) for certain codons over their synonyms.

Exceptions To The Code

The genetic code is almost universal. The same codons are assigned to the same amino acids and to the same START and STOP signals in the vast majority of genes in animals, plants, and microorganisms. However, some exceptions have been found. Most of these involve assigning one or two of the three STOP codons to an amino acid instead.

Mitochondrial genes

When mitochondrial mRNA from animals or microorganisms (but not from plants) is placed in a test tube with the cytosolic protein-synthesizing machinery (amino acids, enzymes, tRNAs, ribosomes) it fails to be translated into a protein.

The reason: these mitochondria use UGA to encode tryptophan (Trp) rather than as a chain terminator. When translated by cytosolic machinery, synthesis stops where Trp should have been inserted.

In addition, most

  • animal mitochondria use AUA for methionine not isoleucine and
  • all vertebrate mitochondria use AGA and AGG as chain terminators.
  • Yeast mitochondria assign all codons beginning with CU to threonine instead of leucine (which is still encoded by UUA and UUG as it is in cytosolic mRNA).

Plant mitochondria use the universal code, and this has permitted angiosperms to transfer mitochondrial genes to their nucleus with great ease.

Nuclear genes

Violations of the universal code are far rarer for nuclear genes.

A few unicellular eukaryotes, notably among the ciliates, have been found that use one or two or even all three of their STOP codons for amino acids. Only those STOP codons occurring close to the poly(A) tail trigger chain termination.

Nonstandard Amino Acids

The vast majority of proteins are assembled from the 20 amino acids listed above even though some of these may be chemically altered, e.g. by phosphorylation, at a later time.

However, two cases have been found where an amino acid that is not one of the standard 20 is inserted by a tRNA into the growing polypeptide.

  • selenocysteine. This amino acid is encoded by UGA. UGA is still used as a chain terminator, but the translation machinery is able to discriminate when a UGA codon should be used for selenocysteine rather than STOP. This codon usage has been found in certain Archaea, eubacteria, and animals (humans synthesize 25 different proteins containing selenium).
  • pyrrolysine. In several species of Archaea and bacteria, this amino acid is encoded by UAG. How the translation machinery knows when it encounters UAG whether to insert a tRNA with pyrrolysine or to stop translation is not yet known.

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