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The Crick papers: 1961 The triplet code
1/3/03. By Giles Newton
Francis Crick, Sydney Brenner and colleagues discover that the genetic code is a triplet code.
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What was the relationship between the sequence of bases in DNA or RNA and the sequence of amino acids in proteins? This question – the genetic code – was the subject of a collaboration between Francis Crick, Sydney Brenner, Leslie Barnett and Watts-Tobin that began in the late 1950s.
In a long series of complex experiments, they induced mutations in the DNA of bacteriophage T4, a virus that infects bacteria. The mutations changed individual bases in the DNA, knocking out the function of a crucial phage gene (the B cistron of the rII region of T4; the mutations were produced by proflavin, which adds or deletes a base rather than changing a base).
When two or four mutations were together, the gene was still inactive, but when three mutations were put together in the same gene, the gene started to work again.
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1 of 4
Triplet Code
Following the initial series of experiments on the triplet code, work continued to provide a more comprehensive genetic map of the rII B cistron of bacteriophage T4 (published in 1967). This genetic map, a 27”x57” sheet of graph paper, is a working draft for this more comprehensive mapping exercise.
Document photographed before conservation.
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2 of 4
Triplet Code
Following the initial series of experiments on the triplet code, work continued to provide a more comprehensive genetic map of the rII B cistron of bacteriophage T4 (published in 1967). This genetic map, a 27”x57” sheet of graph paper, is a working draft for this more comprehensive mapping exercise.
Document photographed before conservation.
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3 of 4
Triplet Code
Following the initial series of experiments on the triplet code, work continued to provide a more comprehensive genetic map of the rII B cistron of bacteriophage T4 (published in 1967). This genetic map, a 27”x57” sheet of graph paper, is a working draft for this more comprehensive mapping exercise.
Document photographed before conservation.
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4 of 4
Triplet Code
Following the initial series of experiments on the triplet code, work continued to provide a more comprehensive genetic map of the rII B cistron of bacteriophage T4 (published in 1967). This genetic map, a 27”x57” sheet of graph paper, is a working draft for this more comprehensive mapping exercise.
Document photographed before conservation.
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They concluded that the genetic code is a triplet code (three bases code for one amino-acid), and that the code is degenerate (an amino-acid may be coded by more than one triplet of bases).
In the 1960s, Marshall Nirenberg and others 'cracked' the code, working out which triplets of nucleotides coded for which amino acids.
"Although Sydney [Brenner] and I clearly realised that the genetic code was a biochemical problem, we still had hopes that genetic methods could contribute to the solution, especially as genetic methods, using the right material, can be very fast...
I often worked through the weekend, taking Monday off so that our laboratory kitchen could catch up. It happened that it was a weekend when I needed a new name, and nobody else was around.
Mutants were usually called by a letter, followed by a number. Thus, P31 meant the thirty-first mutant in the P series, probably produced by proflavin. Unfortunately, I could not remember for certain which letters had already been used, so I decided to rename my mutant FC0, since I was quite sure that no one had used my initials to name mutants...
Carefully we double-checked the numbers on the petri dishes to make sure we had looked at the correct plate. Everything was in order. I looked across at Leslie. 'Do you realise,' I said, 'that you and I are the only people in the world who know it's a triplet code?'"
Crick, 'What Mad Pursuit' (1988), 122, 128, 133.
Further reading
Crick F H C, Barnett L, Brenner S, Watts-Tobin R J (1961) General nature of the genetic code for proteins. Nature 192: 1227-1232.
Barnett L, Brenner S, Crick F H C, Shulman R, Watts-Tobin R J (1967) Phase shift and other mutants in the first part of the rII B cistron of bacteriophage T4. Philos Trans R Soc Lond B Biol Sci 252: 487-560.
