Cracking the genetic code

A review of: The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides. Nirenberg MW, Matthaei JH. Proc Natl Acad Sci U S A. 1961 Oct 15;47(10):1588-602. doi: 10.1073/pnas.47.10.1588.

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The cracking of the genetic code was a team effort but Nirenberg and Matthaei’s experiments published in 1961 were the first step. Francis Crick had conceived the sequence hypothesis – that the sequence of DNA bases determined the sequence of amino acids in a protein. Based on a four-letter genetic code (GCAT) and 20 amino acids, he proposed that the code would be read in triplets, where each triplet coded for one amino acid. However, there was no conclusive experimental evidence supporting that DNA was read in triplets and no idea which triplets coded for which amino acid. Nirenberg and Matthaei employed a cell-free system that could synthesise proteins so that the relationship between RNA and amino acids could be determined. Performing 20 separate experiments, combining a synthetic polyU RNA transcript in a cell free translation system with one of twenty radiolabelled amino acids, they showed a polyU RNA results in a polyphenylalanine protein. Building on the observation that UUU encodes phenylalanine, Nirenberg and Matthaei went on to determine the codons associate with more amino acids, and with the help of others completed the determination of the genetic code. As a result of this work, now the sequence of proteins encoded by DNA and RNA can now be determined.

Creator: Kirby Fahy

References:
Crick, F. H. C., L. Barnett, S. Brenner and R. J. Watts-Tobin, 1961 General Nature of the Genetic Code for Proteins. Nature 192: 1227-1232.
Matthaei, J. H., 0. W. Jones, R. G. Martin and M. W. Nirenberg, 1962 Characteristics and composition of RNA coding units. Proceedings of the National Academy of Sciences of the United
States of America 48: 666-677.
Matthaei, J. H., and M. W. Nirenberg, 1961 Characteristics and stabilization of DNAase-sensitive
protein synthesis in E. coli extracts. Proceedings of the National Academy of Sciences of the United
States of America 47: 1580.
Nirenberg, M. W., and J. H. Matthaei, 1961 The dependence of cell-free protein synthesis in E. coli
upon naturally occurring or synthetic polyribonucleotides. Proceedings of the National Academy of
Sciences of the United States of America 47: 1588-1602.