The Crick, Brenner et al. experiment (1961) was a scientific experiment performed by Francis Crick, Sydney Brenner, 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". [1] This study demonstrated that the genetic code is made up of a series of three base pair codons which code for individual amino acids. The experiment also elucidated the nature of gene expression and frame-shift mutations.
In the experiment, proflavin-induced mutations of the T4 bacteriophage gene, rIIB, were isolated. Proflavin causes mutations by inserting itself between DNA bases, typically resulting in insertion or deletion of a single base pair. [2]
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. [3] This proved that the genetic code uses a codon of three nucleotide bases that corresponds to an amino acid. 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 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. [3]
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. [4]
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. [5]
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. [6] 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. [5]
Francis Harry Compton Crick was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the helical structure of the DNA molecule.
The genetic code is the set of rules used by living cells to translate information encoded within genetic material into proteins. Translation is accomplished by the ribosome, which links proteinogenic amino acids in an order specified by messenger RNA (mRNA), using transfer RNA (tRNA) molecules to carry amino acids and to read the mRNA three nucleotides at a time. The genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries.
The Hershey–Chase experiments were a series of experiments conducted in 1952 by Alfred Hershey and Martha Chase that helped to confirm that DNA is genetic material.
In molecular biology, a stop codon is a codon that signals the termination of the translation process of the current protein. Most codons in messenger RNA correspond to the addition of an amino acid to a growing polypeptide chain, which may ultimately become a protein; stop codons signal the termination of this process by binding release factors, which cause the ribosomal subunits to disassociate, releasing the amino acid chain.
Sydney Brenner 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 on the genetic code, and other areas of molecular biology while working in the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, England. He established the roundworm Caenorhabditis elegans as a model organism for the investigation of developmental biology, and founded the Molecular Sciences Institute in Berkeley, California, United States.
A frameshift mutation is a genetic mutation caused by indels of a number of nucleotides in a DNA sequence that is not divisible by three. Due to the triplet nature of gene expression by codons, the insertion or deletion can change the reading frame, resulting in a completely different translation from the original. The earlier in the sequence the deletion or insertion occurs, the more altered the protein. A frameshift mutation is not the same as a single-nucleotide polymorphism in which a nucleotide is replaced, rather than inserted or deleted. A frameshift mutation will in general cause the reading of the codons after the mutation to code for different amino acids. The frameshift mutation will also alter the first stop codon encountered in the sequence. The polypeptide being created could be abnormally short or abnormally long, and will most likely not be functional.
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 of the 64 triplet codons in the genetic code by using nucleic acid homopolymers to translate specific amino acids.
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 code to be deciphered.
Marshall Warren Nirenberg was an American biochemist and geneticist. He shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" and describing how it operates in protein synthesis. In the same year, together with Har Gobind Khorana, he was awarded the Louisa Gross Horwitz Prize from Columbia University.
Escherichia virus T4 is a species of bacteriophages that infect Escherichia coli bacteria. It is a double-stranded DNA virus in the subfamily Tevenvirinae of the family Straboviridae. T4 is capable of undergoing only a lytic life cycle and not the lysogenic life cycle. The species was formerly named T-even bacteriophage, a name which also encompasses, among other strains, Enterobacteria phage T2, Enterobacteria phage T4 and Enterobacteria phage T6.
In genetics, an insertion is the addition of one or more nucleotide base pairs into a DNA sequence. This can often happen in microsatellite regions due to the DNA polymerase slipping. Insertions can be anywhere in size from one base pair incorrectly inserted into a DNA sequence to a section of one chromosome inserted into another. The mechanism of the smallest single base insertion mutations is believed to be through base-pair separation between the template and primer strands followed by non-neighbor base stacking, which can occur locally within the DNA polymerase active site. On a chromosome level, an insertion refers to the insertion of a larger sequence into a chromosome. This can happen due to unequal crossover during meiosis.
Gene mapping or genome mapping describes the methods used to identify the location of a gene on a chromosome and the distances between genes. Gene mapping can also describe the distances between different sites within a gene.
The history of molecular biology begins in the 1930s with the convergence of various, previously distinct biological and physical disciplines: biochemistry, genetics, microbiology, virology and physics. With the hope of understanding life at its most fundamental level, numerous physicists and chemists also took an interest in what would become molecular biology.
A suppressor mutation is a second mutation that alleviates or reverts the phenotypic effects of an already existing mutation in a process defined synthetic rescue. Genetic suppression therefore restores the phenotype seen prior to the original background mutation. Suppressor mutations are useful for identifying new genetic sites which affect a biological process of interest. They also provide evidence between functionally interacting molecules and intersecting biological pathways.
The phage group was an informal network of biologists centered on Max Delbrück that contributed heavily to bacterial genetics and the origins of molecular biology in the mid-20th century. The phage group takes its name from bacteriophages, the bacteria-infecting viruses that the group used as experimental model organisms. In addition to Delbrück, important scientists associated with the phage group include: Salvador Luria, Alfred Hershey, Seymour Benzer, Charles Steinberg, Gunther Stent, James D. Watson, Frank Stahl, and Renato Dulbecco.
The T4 rII system is an experimental system developed in the 1950s by Seymour Benzer for studying the substructure of the gene. The experimental system is based on genetic crosses of different mutant strains of bacteriophage T4, a virus that infects the bacteria Escherichia coli.
Leslie Barnett was a British biologist who worked with Francis Crick, Sydney Brenner, and Richard J. Watts-Tobin to genetically demonstrate the triplet nature of the code of protein translation through the Crick, Brenner, Barnett, Watts-Tobin et al. experiment of 1961, which discovered frameshift mutations; this insight provided early elucidation of the nature of the genetic code.
The RNA Tie Club was an informal scientific club, meant partly to be humorous, of select scientists who were interested in how proteins were synthesised from genes, specifically the genetic code. It was created by George Gamow upon a suggestion by James Watson in 1954 when the relationship between nucleic acids and amino acids in genetic information was unknown. The club consisted of 20 full members, each representing an amino acid, and four honorary members, representing the four nucleotides. The function of the club members was to think up possible solutions and share with the other members.
The history of genetics can be represented on a timeline of events from the earliest work in the 1850s, to the DNA era starting in the 1940s, and the genomics era beginning in the 1970s.
John Atkins is a research professor at University College Cork and a member of the Royal Irish Academy since 2003. Atkins was the first Irish national to be elected as a member of the EMBO Organization. In 2002 Science Foundation Ireland appointed Atkins as its first Director of Biotechnology. Atkins is also an honorary Professor of Genetics at his alma mater Trinity College, Dublin.