Adaptor hypothesis
Encyclopedia
The adaptor hypothesis is part of a scheme to explain how information encoded in DNA
is used to specify the amino acid sequence of proteins. It was formulated by Francis Crick
in the mid-1950s, together with the central dogma of molecular biology
and the sequence hypothesis
. It first appeared in an informal publication of the RNA Tie Club
in 1955 and was formally published in an article “On Protein Synthesis” in 1958.
Explanation
The adaptor hypothesis was framed to explain how information could be extracted from a nucleic acid
and used to put together a string of amino acids in a specific sequence, that sequence being determined by the nucleotide sequence of the nucleic acid (DNA or RNA
) template. He proposed that each amino acid is first attached to its own specific “adaptor” piece of nucleic acid (in an enzyme
catalysed reaction). The order of assembly of the amino acids is then determined by a specific recognition between the adaptor and the nucleic acid which is serving as the informational template. In this way the amino acids could be lined up by the template in a specific order. Coupling between adjacent amino acids would then lead to the synthesis of a polypeptide whose sequence is determined by the template nucleic acid.
Basis
Crick’s thinking behind this proposal was based on a general consideration of the chemical properties of the two classes of molecule — nucleic acids and proteins. The amino acids are characterised by having a variety of side chains which vary from being hydrophilic to hydrophobic: their individual characters reside in the very different properties these side chains have. By contrast, a nucleic acid is composed of a string of nucleotides whose sequence presents a geometrically defined surface for hydrogen bonding. This makes nucleic acids good at recognising each other, but poor at distinguishing the varied side chains of amino acids. It was this apparent lack of any possibility of specific recognition of amino acid side chains by a nucleotide sequence which led Crick to conclude that amino acids would first become attached to a small nucleic acid — the adaptor — and that this, by base-pairing with the template (presumably as occurs between DNA strands in the double helix), would carry the amino acids to be lined up on the template.
Proof
That such adaptors do exist was discovered by Mahlon Hoagland
and Paul Zamecnik
in 1958. These “soluble RNAs” are now called transfer RNA
s and mediate the translation of messenger RNA
s on ribosomes according to the rules contained in the genetic code
. Crick imagined that his adaptors would be small, perhaps 5-10 nucleotides long. In fact, they are much larger, having a more complex role to play in protein synthesis, and are closer to 100 nucleotides in length.
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
is used to specify the amino acid sequence of proteins. It was formulated by Francis Crick
Francis Crick
Francis Harry Compton Crick OM FRS was an English molecular biologist, biophysicist, and neuroscientist, and most noted for being one of two co-discoverers of the structure of the DNA molecule in 1953, together with James D. Watson...
in the mid-1950s, together with the central dogma of molecular biology
Central dogma of molecular biology
The central dogma of molecular biology was first articulated by Francis Crick in 1958 and re-stated in a Nature paper published in 1970:In other words, the process of producing proteins is irreversible: a protein cannot be used to create DNA....
and the sequence hypothesis
Sequence hypothesis
The sequence hypothesis was first formally proposed in a review “On Protein Synthesis” by Francis Crick in 1958. It states that the sequence of bases in the genetic material determines the sequence of amino acids for which that segment of nucleic acid codes, and this amino acid sequence...
. It first appeared in an informal publication of the RNA Tie Club
RNA Tie Club
The idea of American biologist James D. Watson and Russian-American physicist George Gamow, the RNA Tie Club was a scientific gentleman's club of select members who shared their ideas on how to 'read' the message inside DNA and understand how it relates to proteins...
in 1955 and was formally published in an article “On Protein Synthesis” in 1958.
Explanation
The adaptor hypothesis was framed to explain how information could be extracted from a nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
and used to put together a string of amino acids in a specific sequence, that sequence being determined by the nucleotide sequence of the nucleic acid (DNA or RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
) template. He proposed that each amino acid is first attached to its own specific “adaptor” piece of nucleic acid (in an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
catalysed reaction). The order of assembly of the amino acids is then determined by a specific recognition between the adaptor and the nucleic acid which is serving as the informational template. In this way the amino acids could be lined up by the template in a specific order. Coupling between adjacent amino acids would then lead to the synthesis of a polypeptide whose sequence is determined by the template nucleic acid.
Basis
Crick’s thinking behind this proposal was based on a general consideration of the chemical properties of the two classes of molecule — nucleic acids and proteins. The amino acids are characterised by having a variety of side chains which vary from being hydrophilic to hydrophobic: their individual characters reside in the very different properties these side chains have. By contrast, a nucleic acid is composed of a string of nucleotides whose sequence presents a geometrically defined surface for hydrogen bonding. This makes nucleic acids good at recognising each other, but poor at distinguishing the varied side chains of amino acids. It was this apparent lack of any possibility of specific recognition of amino acid side chains by a nucleotide sequence which led Crick to conclude that amino acids would first become attached to a small nucleic acid — the adaptor — and that this, by base-pairing with the template (presumably as occurs between DNA strands in the double helix), would carry the amino acids to be lined up on the template.
Proof
That such adaptors do exist was discovered by Mahlon Hoagland
Mahlon Hoagland
Mahlon Bush Hoagland is an American biochemist who discovered transfer RNA , the translator of the genetic code.-Early life:Mahlon Bush Hoagland was born in Boston, Massachusetts, U.S. in 1921 to Hudson and Anna Hoagland...
and Paul Zamecnik
Paul Zamecnik
Paul Charles Zamecnik was an American scientist who played a central role in the early history of molecular biology. He was a professor of medicine at Harvard Medical School and a senior scientist at Massachusetts General Hospital. Zamecnik pioneered the in vitro synthesis of proteins and helped...
in 1958. These “soluble RNAs” are now called transfer RNA
Transfer RNA
Transfer RNA is an adaptor molecule composed of RNA, typically 73 to 93 nucleotides in length, that is used in biology to bridge the three-letter genetic code in messenger RNA with the twenty-letter code of amino acids in proteins. The role of tRNA as an adaptor is best understood by...
s and mediate the translation of messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
s on ribosomes according to the rules contained in the genetic code
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
. Crick imagined that his adaptors would be small, perhaps 5-10 nucleotides long. In fact, they are much larger, having a more complex role to play in protein synthesis, and are closer to 100 nucleotides in length.