The Crick, Brenner et al. experiment (1961) was a scientific experiment 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 Nucleic acid doub ...

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 wo ...

, Leslie Barnett 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 Genetic code is a set of rules used by living cell (biology), cells to Translation (biology), translate information encoded within genetic material (DNA or RNA sequences of nucleotide triplets or codons) into proteins. Translation is accomplished ...

is made up of a series of three base pair codons which code for individual

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

. The experiment also elucidated the nature of

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

and frame-shift mutations.

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 antise ...

-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, ...

s of the T4

bacteriophage A bacteriophage (), also known informally as a phage (), is a virus that infects and replicates within bacteria. The term is derived . Bacteriophages are composed of proteins that Capsid, encapsulate a DNA or RNA genome, and may have structu ...

gene, rIIB, were isolated. Proflavin causes mutations by inserting itself between DNA bases, 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 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 over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

. The mutants produced by Crick and Brenner that could not produce functional rIIB protein were the results of frameshift mutations, 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 addition to discovering the triplet nature of the codon, this experiment confirmed the non-overlapping structure of the genetic code, identified the presence of "nonsense coding", and revealed the high degree of degeneracy in codon specification.

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. Decades after its execution, the experiment remains a beacon of inspiration for scientists with its eloquent argumentation and straightforward yet impactful experiments, revealing fundamental insights into living organism organization. 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.

References

Notes

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

The experiment

Implications

See also

References

Notes