for: Introduction to Genetics

The genetic code is the set of rules by which information encoded in genetic material (DNA or RNA sequences) is translated into proteins (amino acid sequences) by living cells. The code defines a mapping between tri-nucleotide sequences, called codons, and amino acids. A triplet codon in a nucleic acid sequence usually specifies a single amino acid (though in some cases the same codon triplet in different locations can code unambiguously for two different amino acids, the correct choice at each location being determined by context). Because the vast majority of genes are encoded with exactly the same code (see the RNA codon table), this particular code is often referred to as the canonical or standard genetic code, or simply the genetic code, though in fact there are many variant codes. Thus the canonical genetic code is not universal. For example, in humans, protein synthesis in mitochondria relies on a genetic code that varies from the canonical code.

It is important to know that not all genetic information is stored using the genetic code. All organisms' DNA contain regulatory sequences, intergenic segments, chromosomal structural areas, which can contribute greatly to phenotype but operate using distinct sets of rules that may or may not be as straightforward as the codon-to-amino acid paradigm that usually underlies the genetic code (see epigenetics).

Cracking the genetic code

After the structure of DNA was deciphered by James Watson, Francis Crick, Maurice Wilkins and Rosalind Franklin, serious efforts to understand the nature of the encoding of proteins began. George Gamow postulated that a three-letter code must be employed to encode the 20 standard amino acids used by living cells to encode proteins (because 3 is the smallest integer n such that 4ⁿ is at least 20).

The fact that codons did consist of three DNA bases was first demonstrated in the Crick, Brenner et al. experiment. The first elucidation of a codon was done by Marshall Nirenberg and Heinrich J. Matthaei in 1961 at the National Institutes of Health. They used a cell-free system to translate a poly-uracil RNA sequence (or UUUUU... in biochemical terms) and discovered that the polypeptide that they had synthesized consisted of only the amino acid phenylalanine. They thereby deduced from this poly-phenylalanine that the codon UUU specified the amino-acid phenylalanine. Extending this work, Nirenberg and Philip Leder were able to elucidate the triplet nature of the genetic code and allowed the codons of the standard genetic code to be deciphered. In these experiments, various combinations of mRNA were passed through a filter which contained ribosomes. Unique triplets promoted the binding of specific tRNAs to the ribosome. Leder and Nirenberg were able to determine the sequences of 54 out of 64 codons.