DNA codes

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 Gamov postulated that a three-letter code must be employed to encode the 20 different amino acids used by living cells to encode proteins (because 3 is the smallest 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 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 his coworkers were able to determine the nucleotide makeup of each codon. In order to determine the order of the sequence, trinucleotides were bound to ribosomes and radioactively labeled aminoacyl-tRNA was used to determine which amino acid corresponded to the codon. Nirenberg's group was able to determine the sequences of 54 out of 64 codons. Subsequent work by Har Gobind Khorana identified the rest of the code, and shortly thereafter Robert W. Holley determined the structure of transfer RNA, the adapter molecule that facilitates translation. This work was based upon earlier studies by Severo Ochoa, who received the Nobel prize in 1959 for his work on the enzymology of RNA synthesis. In 1968, Khorana, Holley and Nirenberg also received the Nobel Prize in Physiology or Medicine for their work