How to synthesise a particular amino acid from the nucleotides of an RNA strand was answered by George Gamow. He suggested that since the mRNA strand consists of only 4 types of nucleotides that code for the 20 amino acids, they need to combine to form a particular code. A single nucleotide would code only four amino acids. Likewise, the combination and permutation of two nucleotides would code for 16 amino acids, while the combination and permutation between three nucleotides would code for 64 amino acids.
The combination of which nucleotides code which amino acid was given by Marshall Nirenberg and Heinrich Matthaei. They grounded E. coli bacteria using mortar and pestle to obtain a free cell system. The E. coli were then added to a test tube containing ribosomes and amino acids required for protein synthesis. Later, artificially synthesised mRNA consisting of only one base, Uracil was added to the test tube. The E. coli extract in the free-cell system was now able to produce a protein chain made of one repeating amino acid phenylealanine, with the help of the Severo Ochoa enzyme, also called polynucleotide phophorylase that was present in the extract. They had finally cracked the genetic code UUU for one amino acid–phenylalanine.
Subsequently, Har Gobind Khorana formulated a chemical method to produce well-defined nucleic acids: long strands of RNA with every nucleotide in the exact position. This helped determine the rest of the genetic code. Today, we know that the genetic code is an array of 64 codons, a sequence of three nucleotides on an RNA strand, which encodes a specific amino acid during protein synthesis. Of the 64 codons, 3 codons–UAA, UAG and UGA act as stop or termination codons, while the rest 61 codons code for 20 amino acids found in the human body. Moreover, one codon codes for only one specific amino acid, like the UGG codes for tryptophan and AUG codes for methionine.
There are different codons encoding a particular amino acid, like serine that is coded by 6 different codons-UCU, UCC, UCA, UCG, AGU and AGC. The genetic code is the same throughout all living organisms, like GUG codes for valine in plants as well as animals. However, there are exceptions such as UGA, which functions as a stop codon in the human cytoplasm but codes for tryptophan in mitochondria.