Early studies on the nature of the genetic code showed that the DNA base sequence corresponds to the amino acid sequence of the polypeptide specified by the gene. That is, the nucleotide and amino acid sequences are colinear. It also became evident that many mutations are the result of changes of single amino acids in a polypeptide chain. However, the exact nature of the code was still unclear.
Establishment of the Genetic Code
- Since only 20 amino acids normally are present in proteins, there must be at least 20 different code words in a linear, single strand of DNA. The code must be contained in some sequence of the four nucleotides commonly found in the linear DNA sequence.
- There are only 16 possible combinations (4²) of the four nucleotides if only nucleotide pairs are considered, not enough to code for all 20 amino acids. Therefore a code word, or codon, must involve at least nucleotide triplets even though this would give 64 possible combinations (4³), many more than the minimum of 20 needed to specify the common amino acids.
- The actual codons were discovered in the early 1960s through the experiments carried out by Marshall Nirenberg, Heinrich Matthaei, Philip Leder, and Har Gobind Khorana. In 1968 Nirenberg and Khorana shared the Nobel prize with
Robert W. Holley, the first person to sequence a nucleic acid (phenylalanyl-tRNA).
Organization of the Code
- The genetic code, presented in RNA form, is summarized in the table. Note that there is code degeneracy. That is, there are up to six different codons for a given amino acid. Only 61 codons, the sense codons, direct amino acid incorporation into protein. The remaining three codons (UGA, UAG, and UAA) are involved in the termination of translation and are called stop or nonsense codons.
- Despite the existence of 61 sense codons, there are not 61 different tRNAs, one for each codon. The 5′ nucleotide in the anticodon can vary, but generally, if the nucleotides in the second and third anticodon positions complement the first two bases of the mRNA codon, an aminoacyl-tRNA with the proper amino acid will bind to the mRNA-ribosome complex. This pattern is evident on inspection of changes in the amino acid specified with variation in the third position. This somewhat loose base pairing is known as wobble and relieves cells of the need to synthesize so many tRNAs. Wobble also decreases the effects of DNA mutations