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The Crick, Brenner et al. experiment (1961) was a
scientific experiment An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a ...
performed by
Francis Crick Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the helical struc ...
,
Sydney Brenner Sydney Brenner (13 January 1927 – 5 April 2019) was a South African biologist. In 2002, he shared the Nobel Prize in Physiology or Medicine with H. Robert Horvitz and Sir John E. Sulston. Brenner made significant contributions to work ...
,
Leslie Barnett Leslie Barnett (born 12 October 1920 as Margaret Leslie Collard – died 10 February 2002) was a British biologist who worked with Francis Crick, Sydney Brenner, and Richard J. Watts-Tobin to genetically demonstrate the genetic code, triplet na ...
and R.J. Watts-Tobin. It was a key experiment in the development of what is now known as molecular biology and led to a publication entitled "The General Nature of the Genetic Code for Proteins" and according to the historian of Science Horace Judson is "regarded...as a classic of intellectual clarity, precision and rigour". This study demonstrated that the
genetic code The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
is made up of a series of three base pair
codon The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
s which code for individual
amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
. The experiment also elucidated the nature of
gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
and
frame-shift mutation A frameshift mutation (also called a framing error or a reading frame shift) is a genetic mutation caused by indels (gene insertion, insertions or genetic deletion, deletions) of a number of nucleotides in a DNA sequence that is not divisible by ...
s.


The experiment

In the experiment,
proflavin Proflavine, also called proflavin and diaminoacridine, is an acriflavine derivative, a disinfectant bacteriostatic against many gram-positive bacteria. It has been used in the form of the dihydrochloride and hemisulfate salts as a topical antisept ...
-induced
mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s of the T4
bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...
gene, rIIB, were isolated. Proflavin causes mutations by inserting itself between
DNA base Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic b ...
s, typically resulting in insertion or deletion of a single base pair. Through the use of proflavin, the experimenters were able to insert or delete base pairs into their sequence of interest. When nucleotides were inserted or deleted, the gene would often be nonfunctional. However, if three base pairs were added or deleted, the gene would remain functional. This proved that the genetic code uses a
codon The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
of three nucleotide bases that corresponds to an
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
. The mutants produced by Crick and Brenner that could not produce functional rIIB protein were the results of
frameshift mutation A frameshift mutation (also called a framing error or a reading frame shift) is a genetic mutation caused by indels ( insertions or deletions) of a number of nucleotides in a DNA sequence that is not divisible by three. Due to the triplet nature ...
s, where the triplet code was disrupted. Brenner and Crick et al. were also able to correct their frameshift mutations through the use of proflavin. If they had a nonfunctional gene due to a deleted base pair, by inserting a
base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
into the general area of the deleted one, they were able to rescue the function of the gene. This is because the bases were shifted back into the correct
reading frame In molecular biology, a reading frame is a way of dividing the nucleic acid sequence, sequence of nucleotides in a nucleic acid (DNA or RNA) molecule into a set of consecutive, non-overlapping triplets. Where these triplets equate to amino acids or ...
.


Implications

This demonstration of the triplet nature of the genetic code, although carried out with bacteriophage, later proved to be universally applicable to all forms of life. The results of this experiment inspired many to begin decoding the triplet code discovered by Brenner and Crick et al. Once this paper was published in 1961, researchers knew that there are 64 possible triplet codons, since there are four nitrogenous bases (4 x 4 x 4 = 64). Today, scientists have decoded what all 64 codons encode for, and the assignments have proven to be nearly universal.


See also

*
Nirenberg and Leder experiment The Nirenberg and Leder experiment was a scientific experiment performed in 1964 by Marshall W. Nirenberg and Philip Leder. The experiment elucidated the triplet nature of the genetic code and allowed the remaining ambiguous codons in the genetic ...
*
Nirenberg and Matthaei experiment The Nirenberg and Matthaei experiment was a scientific experiment performed in May 1961 by Marshall W. Nirenberg and his post-doctoral fellow, J. Heinrich Matthaei, at the National Institutes of Health (NIH). The experiment deciphered the first o ...


Notes


References

* *Sydney Brenner (Author), Lewis Wolpert (Contributor), Errorl C. Friedberg (Contributor), Eleanor Lawrence (Contributor) 2001 My Life in Science: Sydney Brenner, A Life in Science 2001 Biomed Central Ltd (publisher) *Horace Freedland Judson (Author) 1979 The Eighth Day of Creation 1979 Johnathan Cape (publisher) Crick, Brenner et al. experiment, The 1961 in biology {{biochem-stub