Historical review: Deciphering the genetic code--a personal account.

This is an autobiographical description of the events that led to the breaking of the genetic code and the subsequent race to decipher the code. The code was deciphered in two stages over a five-year period between 1961 and 1966. During the first stage, the base compositions of codons were deciphered by the directing cell-free protein synthesis with randomly ordered RNA preparations. During the second phase, the nucleotide sequences of RNA codons were deciphered by determining the species of aminoacyl-tRNA that bound to ribosomes in response to trinucleotides of known sequence. Views on general topics such as how to pick a research problem and competition versus collaboration also are discussed.

[1]  J. Speyer,et al.  Synthetic polynucleotides and the amino acid code. , 1961, Proceedings of the National Academy of Sciences of the United States of America.

[2]  M. Nirenberg,et al.  The dependence of cell-free protein synthesis in E. coli upon RNA prepared from ribosomes. , 1961, Biochemical and biophysical research communications.

[3]  P. Zamecnik,et al.  Amino acid incorporation into protein by extracts of E. coli. , 1960, Biochimica et biophysica acta.

[4]  J. Speyer,et al.  Synthetic polynucleotides and the amino acid code. IV. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[5]  M. Nirenberg,et al.  RNA CODEWORDS AND PROTEIN SYNTHESIS, VI. ON THE NUCLEOTIDE SEQUENCES OF DEGENERATE CODEWORD SETS FOR ISOLEUCINE, TYROSINE, ASPARAGINE, AND LYSINE. , 1965, Proceedings of the National Academy of Sciences of the United States of America.

[6]  A. Kaji,et al.  Specific interaction of soluble RNA with polyribonucleic acid induced polysomes , 1963 .

[7]  J. H. Matthaei,et al.  Approximation of genetic code via cell-free protein synthesis directed by template RNA. , 1963, Federation proceedings.

[8]  M Nirenberg,et al.  RNA codewords and protein synthesis, VII. On the general nature of the RNA code. , 1965, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Speyer,et al.  Synthetic polynucleotides and the amino acid code. V. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Speyer,et al.  Synthetic polynucleotides and the amino acid code. VII. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S. Brenner,et al.  Genetic Code: The ‘Nonsense’ Triplets for Chain Termination and their Suppression , 1965, Nature.

[12]  F. Crick,et al.  UGA: A Third Nonsense Triplet in the Genetic Code , 1967, Nature.

[13]  D. Schlessinger,et al.  AMINO ACID INCORPORATION INTO PROTEINS BY ESCHERICHIA COLI RIBOSOMES. , 1960, Proceedings of the National Academy of Sciences of the United States of America.

[14]  G. Novelli,et al.  The cell-free synthesis of β-galactosidase by escherichia coli , 1960 .

[15]  J. H. Matthaei,et al.  Characteristics and composition of RNA coding units. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Nirenberg,et al.  RNA codons and protein synthesis. IX. Synonym codon recognition by multiple species of valine-, alanine-, and methionine-sRNA. , 1966, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M Nirenberg,et al.  RNA codons and protein synthesis. Xi. Template activity of modified RNA codons. , 1966, Journal of molecular biology.

[18]  Francis Crick,et al.  The Genetic Code , 1962 .

[19]  H. Khorana,et al.  Studies on polynucleotides, XLIX. Stimulation of the binding of aminoacyl-sRNA's to ribosomes by ribotrinucleotides and a survey of codon assignments for 20 amino acids. , 1965, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Nirenberg,et al.  RNA codewords and protein synthesis, 8. Nucleotide sequences of synonym codons for arginine, valine, cysteine, and alanine. , 1965, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Nirenberg,et al.  Degeneracy in the amino acid code. , 1966, Biochimica et biophysica acta.

[22]  ROY MARKHAM,et al.  Structure of Ribonucleic Acid , 1951, Nature.

[23]  Marshall W. Nirenberg,et al.  The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides , 1961, Proceedings of the National Academy of Sciences.

[24]  J. H. Matthaei,et al.  Characteristics and stabilization of DNAase-sensitive protein synthesis in E. coli extracts. , 1961, Proceedings of the National Academy of Sciences of the United States of America.

[25]  L. Heppel,et al.  Nucleotide exchange reactions catalysed by ribonuclease and spleen phosphodiesterase. II. Synthesis of polynucleotides. , 1955, The Biochemical journal.

[26]  R. Brimacombe,et al.  Synthesis of trinucleoside diphosphates with polynucleotide phosphorylase. , 1965, Biochemistry.

[27]  V. A. B. Ėngelʹgardt.  Biological structure and function at the molecular level , 1963 .

[28]  A. Garen,et al.  Base Composition of Nonsense Condons in E. coli: Evidence from Amino-Acid Substitutions at a Tryptophan Site in Alkaline Phosphatase , 1965, Nature.

[29]  L. Astrachan,et al.  Phosphorus incorporation in Escherichia coli ribo-nucleic acid after infection with bacteriophage T2. , 1956, Virology.

[30]  Protein synthesis and the RNA code. , 1965, Harvey lectures.

[31]  B. Clark,et al.  The role of N-formyl-methionyl-sRNA in protein biosynthesis. , 1966, Journal of molecular biology.

[32]  A. D. Hershey,et al.  NUCLEIC ACID ECONOMY IN BACTERIA INFECTED WITH BACTERIOPHAGE T2 , 1953, The Journal of general physiology.

[33]  S. Pestka,et al.  On the Coding of Genetic Information , 1963 .

[34]  M. Nirenberg,et al.  RNA Codewords and Protein Synthesis , 1964, Science.

[35]  M Wilcox,et al.  The RNA code and protein synthesis. , 1966, Cold Spring Harbor symposia on quantitative biology.

[36]  J. H. Matthaei,et al.  Ribonucleotide composition of the genetic code. , 1962, Biochemical and biophysical research communications.

[37]  M. Nirenberg,et al.  RNA CODEWORDS AND PROTEIN SYNTHESIS. II. NUCLEOTIDE SEQUENCE OF A VALINE RNA CODEWORD. , 1964, Proceedings of the National Academy of Sciences of the United States of America.

[38]  F. Crick.  Codon--anticodon pairing: the wobble hypothesis. , 1966, Journal of molecular biology.

[39]  M. Nirenberg,et al.  RNA CODEWORDS AND PROTEIN SYNTHESIS. THE NUCLEOTIDE SEQUENCES OF MULTIPLE CODEWORDS FOR PHENYLALANINE, SERINE, LEUCINE, AND PROLINE. , 1965, Science.

[40]  J. H. Matthaei,et al.  An intermediate in the biosynthesis of polyphenylalanine directed by synthetic template RNA. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Synthetic polynucleotides and the amino acid code. VIII. , 1963, Proceedings of the National Academy of Sciences of the United States of America.

[42]  M. Nirenberg,et al.  Enzymatic utilization of gamma-hydroxybutyric acid. , 1960, The Journal of biological chemistry.

[43]  J. Speyer,et al.  Synthetic polynucleotides and the amino acid code. III. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[44]  M. Nirenberg,et al.  Fine Structure of RNA Codewords Recognized by Bacterial, Amphibian, and Mammalian Transfer RNA , 1967, Science.