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6.3: Genetic Code

Last updated

May 15, 2022
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- 6.2: The Transcription of DNA into RNA
- 6.4: The Translation of RNA into Proteins

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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

Second nucleotide
	U	C	A	G
U	UUU Phenylalanine (Phe)	UCU Serine (Ser)	UAU Tyrosine (Tyr)	UGU Cysteine (Cys)	U
	UUC Phe	UCC Ser	UAC Tyr	UGC Cys	C
	UUA Leucine (Leu)	UCA Ser	UAA STOP	UGA STOP	A
	UUG Leu	UCG Ser	UAG STOP	UGG Tryptophan (Trp)	G
C	CUU Leucine (Leu)	CCU Proline (Pro)	CAU Histidine (His)	CGU Arginine (Arg)	U
	CUC Leu	CCC Pro	CAC His	CGC Arg	C
	CUA Leu	CCA Pro	CAA Glutamine (Gln)	CGA Arg	A
	CUG Leu	CCG Pro	CAG Gln	CGG Arg	G
A	AUU Isoleucine (Ile)	ACU Threonine (Thr)	AAU Asparagine (Asn)	AGU Serine (Ser)	U
	AUC Ile	ACC Thr	AAC Asn	AGC Ser	C
	AUA Ile	ACA Thr	AAA Lysine (Lys)	AGA Arginine (Arg)	A
	AUG Methionine (Met) or START	ACG Thr	AAG Lys	AGG Arg	G
G	GUU Valine Val	GCU Alanine (Ala)	GAU Aspartic acid (Asp)	GGU Glycine (Gly)	U
	GUC (Val)	GCC Ala	GAC Asp	GGC Gly	C
	GUA Val	GCA Ala	GAA Glutamic acid (Glu)	GGA Gly	A
	GUG Val	GCG Ala	GAG Glu	GGG Gly	G

The DNA Codons

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)

TTT	Phe	TCT	Ser	TAT	Tyr	TGT	Cys
TTC	Phe	TCC	Ser	TAC	Tyr	TGC	Cys
TTA	Leu	TCA	Ser	TAA	STOP	TGA	STOP
TTG	Leu	TCG	Ser	TAG	STOP	TGG	Trp
CTT	Leu	CCT	Pro	CAT	His	CGT	Arg
CTC	Leu	CCC	Pro	CAC	His	CGC	Arg
CTA	Leu	CCA	Pro	CAA	Gln	CGA	Arg
CTG	Leu	CCG	Pro	CAG	Gln	CGG	Arg
ATT	Ile	ACT	Thr	AAT	Asn	AGT	Ser
ATC	Ile	ACC	Thr	AAC	Asn	AGC	Ser
ATA	Ile	ACA	Thr	AAA	Lys	AGA	Arg
ATG	Met*	ACG	Thr	AAG	Lys	AGG	Arg
GTT	Val	GCT	Ala	GAT	Asp	GGT	Gly
GTC	Val	GCC	Ala	GAC	Asp	GGC	Gly
GTA	Val	GCA	Ala	GAA	Glu	GGA	Gly
GTG	Val	GCG	Ala	GAG	Glu	GGG	Gly

*When within gene; at beginning of gene, ATG signals where translation of the RNA will begin.

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.One of the reasons is because 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 have been found that use one or two (of their three) STOP codons for amino acids instead.

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.