Central dogma of molecular biology
The central dogma of molecular biology deals with the flow of genetic information within a biological system. It is often stated as "DNA makes RNA, and RNA makes protein",[1] although this is not its original meaning. It was first stated by Francis Crick in 1957,[2][3] then published in 1958:[4][5]
The Central Dogma. This states that once "information" has passed into protein it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information here means the precise determination of sequence, either of bases in the nucleic acid or of amino acid residues in the protein.
He re-stated it in a Nature paper published in 1970: "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."[6]
A second version of the central dogma is popular but incorrect. This is the simplistic DNA → RNA → protein pathway published by James Watson in the first edition of The Molecular Biology of the Gene (1965). Watson's version differs from Crick's because Watson describes a two-step (DNA → RNA and RNA → protein) process as the central dogma.[7] While the dogma as originally stated by Crick remains valid today,[6][8] Watson's version does not.[2]
Biological sequence information
The
General transfers of biological sequential information
Table of the three classes of information transfer. General Special Unknown DNA → DNA RNA → DNA Protein → DNA DNA → RNA RNA → RNA Protein → RNA RNA → protein Protein → protein DNA → protein
DNA replications
In the sense that DNA replication must occur if genetic material is to be provided for the progeny of any cell, whether somatic or reproductive, the copying from DNA to DNA arguably is the fundamental step in information transfer. A complex group of proteins called the replisome performs the replication of the information from the parent strand to the complementary daughter strand.
Transcription
Transcription is the process by which the information contained in a section of DNA is replicated in the form of a newly assembled piece of
occurs when appropriate, increasing the diversity of the proteins that any single mRNA can produce. The product of the entire transcription process (that began with the production of the pre-mRNA chain) is a mature mRNA chain.Translation
The mature mRNA finds its way to a
The mRNA does not contain all the information for specifying the nature of the mature protein. The nascent polypeptide chain released from the ribosome commonly requires additional processing before the final product emerges. For one thing, the correct folding process is complex and vitally important. For most proteins it requires other
Special transfers of biological sequential information
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, as well as in eukaryotes, in the case of retrotransposons and telomere synthesis. It is the process by which genetic information from RNA gets transcribed into new DNA. The family of enzymes involved in this process is called Reverse Transcriptase.
RNA replication
RNA replication is the copying of one RNA to another. Many viruses replicate this way. The enzymes that copy RNA to new RNA, called RNA-dependent RNA polymerases, are also found in many eukaryotes where they are involved in RNA silencing.[11]
RNA editing, in which an RNA sequence is altered by a complex of proteins and a "guide RNA", could also be seen as an RNA-to-RNA transfer.
Direct translation from DNA to protein
Direct translation from DNA to protein has been demonstrated in a cell-free system (i.e. in a test tube), using extracts from E. coli that contained ribosomes, but not intact cells. These cell fragments could synthesize proteins from single-stranded DNA templates isolated from other organisms (e.g., mouse or toad), and neomycin was found to enhance this effect. However, it was unclear whether this mechanism of translation corresponded specifically to the genetic code.[12][13]
Transfers of information not explicitly covered in the theory
Post-translational modification
After protein amino acid sequences have been translated from nucleic acid chains, they can be edited by appropriate enzymes. Although this is a form of protein affecting protein sequence, not explicitly covered by the central dogma, there are not many clear examples where the associated concepts of the two fields have much to do with each other.
Inteins
An intein is a "parasitic" segment of a protein that is able to excise itself from the chain of amino acids as they emerge from the ribosome and rejoin the remaining portions with a peptide bond in such a manner that the main protein "backbone" does not fall apart. This is a case of a protein changing its own primary sequence from the sequence originally encoded by the DNA of a gene. Additionally, most inteins contain a homing endonuclease or HEG domain which is capable of finding a copy of the parent gene that does not include the intein nucleotide sequence. On contact with the intein-free copy, the HEG domain initiates the DNA double-stranded break repair mechanism. This process causes the intein sequence to be copied from the original source gene to the intein-free gene. This is an example of protein directly editing DNA sequence, as well as increasing the sequence's heritable propagation.
Methylation
Variation in
Prions
Some scientists such as Alain E. Bussard and Eugene Koonin have argued that prion-mediated inheritance violates the central dogma of molecular biology.[14][15] However, Rosalind Ridley in Molecular Pathology of the Prions (2001) has written that "The prion hypothesis is not heretical to the central dogma of molecular biology—that the information necessary to manufacture proteins is encoded in the nucleotide sequence of nucleic acid—because it does not claim that proteins replicate. Rather, it claims that there is a source of information within protein molecules that contributes to their biological function, and that this information can be passed on to other molecules."[16]
Natural genetic engineering
James A. Shapiro argues that a superset of these examples should be classified as natural genetic engineering and are sufficient to falsify the central dogma. While Shapiro has received a respectful hearing for his view, his critics have not been convinced that his reading of the central dogma is in line with what Crick intended.[17][18]
Use of the term dogma
In his
"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."
Similarly, Horace Freeland Judson records in The Eighth Day of Creation:[19]
"My mind was, that a dogma was an idea for which there was no reasonable evidence. You see?!" And Crick gave a roar of delight. "I just didn't know what dogma meant. And I could just as well have called it the 'Central Hypothesis,' or — you know. Which is what I meant to say. Dogma was just a catch phrase."
Comparison with the Weismann barrier
The
See also
- Life
- Cell (biology)
- Cell division
- Gene
- Gene expression
- Epigenetics
- Genome
- Alternative splicing
- Genetic code
- Riboswitch
References
- ^ Leavitt SA (June 2010). "Deciphering the Genetic Code: Marshall Nirenberg". Office of NIH History. Archived from the original on 2015-03-17. Retrieved 2012-03-02.
- ^ PMID 28922352.
- ^ "CSHL Archives Repository | On Protein Synthesis". libgallery.cshl.edu. Retrieved 2018-11-13.
- ^ Crick FH (1958). "On Protein Synthesis". In F. K. Sanders (ed.). Symposia of the Society for Experimental Biology, Number XII: The Biological Replication of Macromolecules. Cambridge University Press. pp. 138–163.
- PMID 13580867.
- ^ S2CID 4164029.
- ^ Moran LA (15 January 2007). "Sandwalk: Basic Concepts: The Central Dogma of Molecular Biology". sandwalk.blogspot.com. Retrieved 17 March 2018.
- ISBN 978-0-465-06267-6.
When Crick enuciated the central dogma, his aim was not to reframe Weismann's division of cells into the somatic line and the germ line, or to defend the modern understanding of evolution by natural selection against the idea of the inheritance of acquired characteristics. The central dogma was based on known or assumed patterns of biochemical information transfer in the cell rather than any dogmatic position. As such it was vulnerable to being invalidated by future discoveries. Nevertheless, in its fundamentals it has been shown to be correct. Real or apparent exceptions to this rule, such as retrotranscription prion disease or transgenerational epigenetic effects have not undermined its basic truth. (p. 263)
- )
- ^ Elzanowski A, Ostell J (2008-04-07). "The Genetic Codes". National Center for Biotechnology Information (NCBI). Retrieved 2021-08-03.
- S2CID 42526536.
- PMID 4955657.
- PMID 12038981.
- PMID 16065057.
- PMID 22913395.
- ISBN 0-89603-924-2.
- PMC 3342868.
- ^ Moran LA (May–June 2011). "(Review) Evolution: A View from the 21st Century". Reports of the National Center for Science Education. 32.3 (9): 1–4. Archived from the original on 2013-09-15. Retrieved 2012-10-27.
- ISBN 978-0-87969-477-7.
- S2CID 85866639.
- ISBN 978-0-7391-7436-4.)
Where Weismann would say that it is impossible for changes acquired during an organism's lifetime to feed back onto transmissible traits in the germ line, the CDMB now added that it was impossible for information encoded in proteins to feed back and affect genetic information in any form whatsoever, which was essentially a molecular recasting of the Weismann barrier.
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Further reading
- Bussard AE (August 2005). "A scientific revolution? The prion anomaly may challenge the central dogma of molecular biology". EMBO Reports. 6 (8): 691–4. PMID 16065057.
- Baker, Harry F. (2001). Molecular Pathology of the Prions (Methods in Molecular Medicine). Humana Press. ISBN 0-89603-924-2
- Li JJ, Biggin MD (March 2015). "Gene expression. Statistics requantitates the central dogma". Science. 347 (6226): 1066–7. PMID 25745146.
- Piras V, Tomita M, Selvarajoo K (2012). "Is central dogma a global property of cellular information flow?". Frontiers in Physiology. 3: 439. PMID 23189060.
- Robinson VL (2009). "Rethinking the central dogma: noncoding RNAs are biologically relevant". Urologic Oncology. 27 (3): 304–6. PMID 19414118.
External links
- The Elaboration of the Central Dogma – Scitable: By Nature education
- Animation of Central Dogma from RIKEN - NatureDocumentaries.org
- Discussion on challenges to the "Central Dogma of Molecular Biology"
- Explanation of the central dogma using a musical analogy
- "Francis Harry Compton Crick (1916–2004)" by A. Andrei at the Embryo Project Encyclopedia