Central dogma of molecular biology
From Wikipedia, the free encyclopedia
The central dogma of molecular biology was first enunciated by Francis Crick in 1958 <ref name="crick1958">Crick, F.H.C., 1958 On Protein Synthesis. in Symp. Soc. Exp. Biol. XII, 139-163. (pdf, early draft of original article) </ref> and re-stated in a Nature paper published in 1970 <ref name="crick1970">Crick, F., 1970, Central Dogma of Molecular Biology. Nature 227, 561-563 </ref>:
- The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred back from protein to either protein or nucleic acid.
In other words, 'once information gets into protein, it can't flow back to nucleic acid.'
The dogma is a framework for understanding the transfer of sequence information between sequential information-carrying biopolymers, in the most common or general case, in living organisms. There are 3 major classes of such biopolymers: DNA and RNA (both nucleic acids), and protein. There are 3×3 = 9 conceivable direct transfers of information that can occur between these. The dogma classes these into 3 groups of 3: 3 general transfers (believed to occur normally in most cells), 3 special transfers (known to occur, but only under abnormal conditions), and 3 unknown transfers (believed to never occur). The general transfers describe the normal flow of biological information: DNA can be copied to DNA (DNA replication), DNA information can be copied into mRNA, (transcription), and proteins can be synthesized using the information in mRNA as a template (translation) <ref name="crick1970"/>.
The central dogma is occasionally misunderstood as being a statement of absolute fact. If taken as such, it can be criticised, as there are well-described exceptions. It is also criticised by some systems biologists as being too reductionist.
[edit] Biological sequence information
- Main article: Primary structure
Biopolymers are biological polymers. That is, they are molecules made up of building blocks known as monomers. The biopolymers DNA, RNA and proteins, are linear polymers (ie: each monomer connects to at most two other monomers). The sequence, or arrangement of their monomers, effectively encodes information. The transfers of information described by the central dogma are faithful, deterministic transfers, wherein one biopolymer's sequence is used as a template for the construction of another biopolymer with a sequence that is entirely dependent on the original biopolymer's.
[edit] General transfers of biological sequential information
| General | Special | Unknown |
|---|---|---|
| DNA → DNA | RNA → DNA | protein → DNA |
| DNA → RNA | RNA → RNA | protein → RNA |
| RNA → protein | DNA → protein | protein → protein |
[edit] DNA Replication
Finally, as the final step in the Central Dogma, to transmit the genetic information between parents and progeny, the DNA must be replicated faithfully. Replication is carried out by a complex group of proteins that unwind the superhelix, unwind the double-stranded DNA helix, and, using DNA polymerase and its associated proteins, copy or replicate the master template itself so the cycle can repeat DNA → RNA → protein in a new generation of cells or organisms.
[edit] Transcription
Transcription is the process by which the information contained in a section of DNA is transferred to a newly assembled piece of messenger RNA (mRNA). It is facilitated by RNA polymerase and transcription factors. In eukaryote cells the primary transcript (pre-mRNA) is often processed further via alternative splicing. In this process, blocks of mRNA are cut out and rearranged, to produce different arrangements of the original sequence.
[edit] Translation
Eventually, this mature mRNA finds its way to a ribosome, where it is translated. In prokaryotic cells, which have no nuclear compartment, the process of transcription and translation may be linked together. In eukaryotic cells, the site of transcription (the cell nucleus) is usually separated from the site of translation (the cytoplasm), so the mRNA must be transported out of the nucleus into the cytoplasm, where it can be bound by ribosomes. The mRNA is read by the ribosome as triplet codons, usually beginning with an AUG, or initiator methonine codon downstream of the ribosome binding site. Complexes of initiation factors and elongation factors bring aminoacylated transfer RNAs (tRNAs) into the ribosome-mRNA complex, matching the codon in the mRNA to the anti-codon in the tRNA, thereby adding the correct amino acid in the sequence encoding the gene. As the amino acids are linked into the growing peptide chain, they begin folding into the correct conformation. This folding continues until the nascent polypeptide chains are released from the ribosome as a mature protein. In some cases the new polypeptide chain requires additional processing to make a mature protein. The correct folding process is quite complex and may require other proteins, called chaperone proteins. Occasionally proteins themselves can be further spliced, when this happens the inside "discarded" section is known as an intein.
[edit] Special transfers of biological sequential information
[edit] Reverse transcription
Reverse transcription is the transfer of information from RNA to DNA (the reverse of normal transcription). This is known to occur in the case of retroviruses, such as HIV, and, in higher eukaryotes, in the case of retrotransposons. It is not, however, the general case in most living organisms.
[edit] RNA replication
RNA replication is the copying of one RNA to another. It is possible that this is the mechanism by which some RNA viruses replicate <ref name="crick1970"/>.
[edit] Direct translation from DNA to protein
This has been shown to occur in a cell-free system (ie: in a test tube), using neomycin<ref name="crick1970"/>.
[edit] Prions - almost an "unknown transfer"
Prions are proteins that propagate themselves by making conformational changes in other molecules of the same type of protein. This change affects the behaviour of the protein. In fungi this change can be passed from one generation to the next, i.e. Protein → Protein. Although this represents a transfer of information, it is not an exception to the central dogma, since the sequence of the protein remains unchanged.
[edit] Use of the term "dogma"
In his autobiography, What Mad Pursuit, Crick wrote about his choice of the word dogma and some of the problems it caused him:
- I called this idea the central dogma, for two reasons, I suspect. I had already used the obvious word hypothesis in the sequence hypothesis, and in addition I wanted to suggest that this new assumption was more central and more powerful. ... As it turned out, the use of the word dogma caused almost more trouble than it was worth.... Many years later Jacques Monod pointed out to me that I did not appear to understand the correct use of the word dogma, which is a belief that cannot be doubted. I did apprehend this in a vague sort of way but since I thought that all religious beliefs were without foundation, I used the word the way I myself thought about it, not as most of the world does, and simply applied it to a grand hypothesis that, however plausible, had little direct experimental support.
[edit] Criticisms of the use of the central dogma as a research strategy
Some researchers in the area of systems biology claim that scientists sometimes misuse the central dogma as a research strategy. They claim that an uncritical reading of the central dogma could inhibit novel approaches to understanding multicellular development of organisms as well as multicellular diseases; that the central dogma is often used as a reductionist research strategy that proceeds bottom up, attempting to explain all biological phenomena in molecular terms. Although they don't dispute the very specific reading of the central dogma, these researchers claim that a reductionist research strategy may limit the understanding of complex systems that cannot be analyzed by their molecular interactions alone because of the combinatorial complexity involved <ref name="werner">Werner, E., 2005, Genome Semantics, In Silico Multicellular Systems and the Central Dogma, FEBS Letters 579, pp 1779-1782 (March 21, 2005) </ref>
[edit] See also
[edit] References
<references/>
[edit] External links
- Central Dogma : Article from Knowmed Article Repository: A history of the development of the dogma, listing a few key experimentsde:Ein-Gen-ein-Enzym-Hypothese
el:Κεντρικό δόγμα Mοριακής Bιολογίας fr:Central dogma ko:분자생물학의 중심원리 ja:セントラルドグマ ru:Реализация генетической информации sv:Centrala dogmen vi:Luận thuyết trung tâm zh:中心法則
