The Genetic Code and Translation into Proteins

Translation is the process in which a ribosome reads the codons of a messenger RNA and builds a protein by joining amino acids in the order specified by the genetic code. In brief: the genetic code is a set of 64 three-base codons: 61 code for amino acids, and 3 are stop signals. AUG is the start codon and codes for methionine. Each transfer RNA has an anticodon that pairs with a codon and carries the matching amino acid.

Translation turns the information carried in mRNA into the proteins that do the work of the cell. This guide explains the properties of the genetic code, shows the full codon table, describes the roles of tRNA and the ribosome, follows the three stages of translation, works through the translation of a short mRNA step by step and corrects common mistakes.

What is the genetic code?

The genetic code is the set of rules by which the sequence of bases in mRNA is translated into the sequence of amino acids in a protein. It has these properties:

• Triplet: three bases (a codon) code for one amino acid. With four bases, there are 4³ = 64 possible codons, more than enough for the 20 amino acids. Two-base codons would give only 4² = 16, not enough.
• Degenerate (redundant): most amino acids are coded by more than one codon. For example, leucine has six. The third base of the codon often varies without changing the amino acid, which reduces the effect of some mutations.
• Unambiguous: each codon codes for only one amino acid (or a stop signal).
• Non-overlapping and continuous: codons are read in sequence, three bases at a time, without gaps or overlaps. The group of three that is used is the reading frame.
• Nearly universal: the same code is used by almost all organisms, from bacteria to humans, which supports common ancestry and allows genes to be transferred between species in genetic engineering. There are small variants, for example in mitochondria.

There are special codons. AUG is the start codon and also codes for methionine. UAA, UAG and UGA are stop codons, which do not code for an amino acid and cause the release of the finished protein.

The codon table

The table lists each amino acid with the mRNA codons that code for it. All 64 codons are included: 61 for amino acids and 3 stop codons.

Check: 2 + 6 + 3 + 1 + 4 + 6 + 4 + 4 + 4 + 2 + 2 + 2 + 2 + 2 + 2 + 2 + 2 + 1 + 6 + 4 + 3 = 64.

Which molecules take part in translation?

• mRNA: the template that carries the codons.
• tRNA: each tRNA has an anticodon, a sequence of three bases complementary to a codon, and carries the corresponding amino acid on its other end. Enzymes called aminoacyl-tRNA synthetases attach the correct amino acid to each tRNA, which ensures accuracy. The anticodon pairs with the codon by complementary base pairing, antiparallel, so the anticodon for AUG is UAC.
• Ribosome: a complex of rRNA and proteins with two subunits (large and small). It has three sites for tRNA: A (aminoacyl), P (peptidyl) and E (exit).
• Energy and factors: GTP supplies energy, and initiation, elongation and release factors help.

What are the stages of translation?

1. Initiation: the small ribosomal subunit binds to the mRNA near the 5′ end and scans until it finds the start codon AUG. The initiator tRNA, carrying methionine, pairs with AUG in the P site. The large subunit then joins.
2. Elongation: a tRNA with the anticodon complementary to the next codon enters the A site. The ribosome forms a peptide bond between the amino acid in the P site and the one in the A site, transferring the growing chain to the tRNA in the A site. The ribosome then moves along the mRNA by one codon (translocation). The empty tRNA leaves from the E site, and the cycle repeats. A ribosome adds about 15 to 20 amino acids per second in bacteria and about 5 per second in eukaryotes.
3. Termination: when a stop codon reaches the A site, a release factor binds. The polypeptide is released, and the ribosome subunits separate.

Many ribosomes can translate the same mRNA at the same time, forming a polyribosome (polysome), so many copies of the protein are made quickly. In eukaryotes, proteins that are to be secreted are made by ribosomes attached to the rough endoplasmic reticulum.

Worked example: translating an mRNA

Translate the following mRNA: 5′-AUGGCUUGGAAAUGA-3′.

1. Find the reading frame: start at the first AUG. Split into codons: AUG | GCU | UGG | AAA | UGA.
2. Look up each codon: AUG = methionine (Met); GCU = alanine (Ala); UGG = tryptophan (Trp); AAA = lysine (Lys); UGA = stop.
3. Write the polypeptide: Met–Ala–Trp–Lys, 4 amino acids.
4. Peptide bonds: 4 amino acids are joined by 3 peptide bonds.
5. Anticodons: for AUG, the tRNA anticodon is UAC; for GCU it is CGA; for UGG it is ACC; for AAA it is UUU (each written 3′ to 5′ on the tRNA, to pair with the codon read 5′ to 3′).

The mRNA has 15 bases. The 5 codons include the stop codon, which is why the protein has 4 amino acids, one fewer than the number of codons. The rule is: amino acids = (number of bases ÷ 3) − 1 for a sequence ending in a stop codon. The check: 15 ÷ 3 − 1 = 4. If a mutation changed the second codon to UAA, the protein would be only 1 amino acid long (Met), because translation would stop at this codon. The effects of mutations on the protein are discussed in the next article.

How was the code cracked?

In 1961, Marshall Nirenberg and Heinrich Matthaei showed that a synthetic RNA made only of uracil (poly-U) produced a protein made only of phenylalanine, which meant that UUU codes for phenylalanine. This was the first codon to be identified. Nirenberg, Har Gobind Khorana and Robert Holley worked out the complete code by 1966, and they shared the 1968 Nobel Prize in Physiology or Medicine. Francis Crick and Sydney Brenner had earlier shown that the code is based on triplets, using mutations in bacterial viruses. The ribosome structure was solved in 2000 by teams led by Venki Ramakrishnan, Thomas Steitz and Ada Yonath, who shared the Nobel Prize in Chemistry in 2009.

What happens to the protein afterwards?

The polypeptide folds into its three-dimensional shape, sometimes with the help of proteins called chaperones. It may be chemically modified, cut or combined with other polypeptides. Signals within the protein send it to its correct location. Misfolded proteins are normally degraded, and a build-up of misfolded proteins is associated with some diseases.

Which mistakes are common?

Mistake 1: Translating the DNA sequence directly with the codon table

The table is for mRNA codons. If you start with the template strand, first find the mRNA.

Mistake 2: Confusing codon and anticodon

The codon is on the mRNA. The anticodon is on the tRNA and is complementary to the codon.

Mistake 3: Counting the stop codon as an amino acid

Stop codons do not code for amino acids, so the protein is one amino acid shorter than the number of codons.

Mistake 4: Reading the mRNA in the wrong direction

The mRNA is read 5′ to 3′. Always start at the start codon, and keep the reading frame.