The instructions for building proteins, the building blocks of cells, are encoded in genes. Each group of three DNA letters encodes one amino acid, and there are 64 different combinations of these groups (called codons) that correspond to 20 amino acids and a stop signal. Marshall Nirenberg cracked the code that translates DNA code information into proteins by using synthetic RNA chains to instruct them to add amino acids. His discovery earned him a Nobel Prize in 1968.

Codons

In the genetic code, codons are sequences of three DNA bases that specify an amino acid. The same code is used in all organisms and organelles (with some exceptions). This code determines what amino acids are encoded by a gene, which sequence of bases translates into mRNA, and how proteins are made from this mRNA.

In mRNA, a codon pairs with a complementary base in tRNA to determine which amino acid is added to the growing protein chain. The start and stop signals for protein synthesis are also determined by codons.

Due to the degeneracy of the genetic code, most amino acids are encoded by more than one codon. However, different sequences that produce identical proteins may have slightly different codon usage patterns, and this is known as codon bias. This variation is believed to result from the combined effects of mutation, natural selection and random genetic drift. This codon usage bias can influence protein folding, cellular functions and genome evolution.

Amino Acids

The coding strand of DNA encodes three-letter sequences that correspond to particular amino acids when building protein chains. Each sequence is known as a codon, and the set of codes is called the genetic code.

Marshall Nirenberg and Heinrich Matthaei first deciphered the genetic code in 1961 by analyzing a poly-uracil RNA molecule. They found that every sequence of three nucleotide bases could be read in one of three ways, producing a possible amino acid sequence.

The standard genetic code contains 64 possible combinations of three codons, or triplets. Using the standard codon table, each triplet is translated into an amino acid and the appropriate signal if it is a start or stop codon. Most amino acids require multiple codons to specify, a feature of the code called degeneracy. Leucine, Thr, Val, and Ile each require four codons; Serine requires five; and Asparagine and His require six. Amino acids are strung together in long, unbranched chains that make up proteins, which perform many essential biological functions.

Stop Signals

A sequence of three nucleotide bases (or trinucleotides) in mRNA that does not code for an amino acid is called a stop codon. These codons are the end of a gene’s protein instructions and signal that the ribosome should stop adding amino acids to the growing polypeptide chain. There are 64 possible codon combinations in a gene, and 61 of them specify amino acids; the remaining three codons are stop signals.

In eukaryotes, the stop codons are UAA, UAG, and UGA. If a ribosome reaches one of these codons, it will normally stop protein synthesis; however, occasionally, a ribosome bypasses a stop codon and continues translation. This process is called “readthrough.” It can be induced by viruses or by the use of certain drugs (e.g., gentamycin).

A key step in stop codon recognition is the recognition of a peptide anticodon by the ribosomal initiation factor eRF1. The first base in a stop codon contacts the conserved residue Ile62 in eRF1’s a2-loop-a3 structural motif. This residue interacts with the thymine in tRNA, which acts as the anticodon during protein synthesis.

Translation

The code for amino acid sequences is decoded in a ribosome in the cell cytoplasm. Each mRNA codon is translated into a chain of amino acids that folds to form a protein.

The ribosome begins at the start codon, a group of three nucleotides that corresponds to the first tRNA anticodon sequence. The first tRNA binds to the mRNA, carries the amino acid it is designated for, and then joins the growing polypeptide chain by bonding with it (elongation). It continues to read each successive codon until reaching a stop codon, which signals that the tRNA should be released from the ribosome.

Marshall Nirenberg and Heinrich Matthaei were the first to reveal that a codon was like a three-letter word, with each codon specifying one of 64 possible amino acids. 61 of these code for the amino acids that make up proteins. The rest code for other cellular functions. The standard genetic code applies to all living organisms and is a powerful proof of the common ancestry of life on Earth.