Editing Central dogma of molecular biology

{{short description|Explanation of the flow of genetic information within a biological system}}
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",<ref name="Leavitt">{{cite web | last=Leavitt | first=Sarah A. | name-list-style=vanc | title=Deciphering the Genetic Code: Marshall Nirenberg | publisher=Office of NIH History | date=June 2010 | url=http://history.nih.gov/exhibits/nirenberg/glossary.htm | access-date=2012-03-02 | archive-url=https://web.archive.org/web/20150317004800/http://history.nih.gov/exhibits/nirenberg/glossary.htm | archive-date=2015-03-17 | url-status=dead }}</ref> although this is not its original meaning. It was first stated by [[Francis Crick]] in 1957,<ref name="Cobb 2017">{{cite journal | vauthors = Cobb M | title = 60 years ago, Francis Crick changed the logic of biology | journal = PLOS Biology | volume = 15 | issue = 9 | pages = e2003243 | date = September 2017 | pmid = 28922352 | pmc = 5602739 | doi = 10.1371/journal.pbio.2003243 | doi-access = free }}</ref><ref>{{Cite web|url=http://libgallery.cshl.edu/items/show/52220|title=CSHL Archives Repository {{!}} On Protein Synthesis|website=libgallery.cshl.edu|language=en-US|access-date=2018-11-13}}</ref> then published in 1958:<ref name="crick1956">{{cite book | vauthors = Crick FH |author-link=Francis Crick |chapter=On Protein Synthesis |editor= F. K. Sanders |title=Symposia of the Society for Experimental Biology, Number XII: The Biological Replication of Macromolecules |date=1958 |publisher=Cambridge University Press |pages=138–163}}</ref><ref>{{Cite journal |url=https://wellcomelibrary.org/item/b1817789x |title=On protein synthesis |last=Crick |first=Francis. H. C. |date=1958 |journal=Symposia of the Society for Experimental Biology |volume=12 |publisher=Symposia on the society for Experimental biology number XII: The Biological Replication of Macromolecules |pmid=13580867 |at=p. 153 }}</ref>

{{blockquote|text=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 (journal)|Nature]]'' paper published in 1970: "The central dogma of [[molecular biology]] deals with the detailed [[residue (chemistry)#Biochemisty|residue]]-by-residue transfer of [[DNA sequencing|sequential information]]. It states that such information cannot be transferred back from protein to either protein or nucleic acid."<ref name="crick1970">{{cite journal | vauthors = Crick F | title = Central dogma of molecular biology | journal = Nature | volume = 227 | issue = 5258 | pages = 561–3 | date = August 1970 | pmid = 4913914 | doi = 10.1038/227561a0 | url = https://www.nature.com/articles/227561a0 | author-link = Francis Crick | bibcode = 1970Natur.227..561C | s2cid = 4164029 }}</ref>

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.<ref>{{cite web |url=http://sandwalk.blogspot.com/2007/01/central-dogma-of-molecular-biology.html |title=Sandwalk: Basic Concepts: The Central Dogma of Molecular Biology |first=Laurence A. |last=Moran | name-list-style = vanc |date=15 January 2007 |website=sandwalk.blogspot.com |access-date=17 March 2018}}</ref> While the dogma as originally stated by Crick remains valid today,<ref name="crick1970" /><ref>{{cite book | last = Cobb | first = Matthew |title=Life's Greatest Secret: The Race to Crack the Genetic Code |year=2015 |publisher=Basic Books |isbn=978-0-465-06267-6 |quote=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)}}</ref> Watson's version does not.<ref name="Cobb 2017" />

== Biological sequence information ==
{{Main|Primary structure}}

The [[biopolymer]]s that comprise DNA, RNA and (poly)[[peptide]]s are linear heteropolymers (i.e.: each [[monomer]] is connected to at most two other monomers). The [[sequence (biology)|sequence]] of their monomers effectively encodes information. The transfers of information from one molecule to another 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 sequence. When DNA is transcribed to RNA, its complement is paired to it. DNA codes are transferred to RNA codes in a complementary fashion. The encoding of proteins is done in groups of three, known as [[Genetic code|codons]]. The [[DNA and RNA codon tables|standard codon table]] applies for humans and mammals, but some other lifeforms (including human mitochondria<ref>{{cite journal |vauthors=Barrell BG, Bankier AT, Drouin J |date=1979 |title=A different genetic code in human mitochondria |journal=Nature |volume=282 |issue=5735 |pages=189–194 |bibcode=1979Natur.282..189B |doi=10.1038/282189a0 |pmid=226894 |s2cid=4335828}} ([https://www.ncbi.nlm.nih.gov/pubmed/226894])</ref>) use different [[List of genetic codes|translations]].<ref>{{cite web |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi?mode=c |title=The Genetic Codes |vauthors=Elzanowski A, Ostell J |date=2008-04-07| publisher=National Center for Biotechnology Information (NCBI) |access-date = 2021-08-03}}</ref>

== General transfers of biological sequential information ==
[[File:Crick's 1958 central dogma.svg|left|thumb|247x247px|Francis Crick's 1958 figure showing various information transfers]]

=== DNA replications ===
{{Main|DNA replication|Replisome}}

In the sense that DNA replication must occur if genetic material is to be provided for the [[Offspring|progeny]] of any cell, whether [[Somatic cell|somatic]] or [[Germ cell|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 ===
[[File:Central Dogma of Molecular Biochemistry with Enzymes.jpg|right|thumb |256px]]
{{Main|Transcription (biology)}}

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 [[messenger RNA]] (mRNA). Enzymes facilitating the process include [[RNA polymerase]] and [[transcription factor]]s. In [[eukaryote|eukaryotic]] cells the primary transcript is [[Precursor mRNA|pre-mRNA]]. Pre-mRNA must be [[post-transcriptional modification|processed]] for translation to proceed. Processing includes the addition of a [[5' cap]] and a [[polyadenylation|poly-A tail]] to the pre-mRNA chain, followed by [[RNA splicing|splicing]]. [[Alternative splicing]] 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.{{cn|date=April 2025}}

=== Translation ===
{{Main|Translation (biology)}}

The mature mRNA finds its way to a [[ribosome]], where it gets [[translation (genetics)|translated]]. In [[prokaryotic]] cells, which have no nuclear compartment, the processes of transcription and translation may be linked together without clear separation. 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 ribosome reads the mRNA triplet [[genetic code|codons]], usually beginning with an AUG ([[adenine]]−[[uracil]]−[[guanine]]), or initiator [[methionine]] codon downstream of the [[ribosome]] binding site. Complexes of [[initiation factor]]s and [[elongation factor]]s bring [[aminoacylation|aminoacylated]] [[transfer RNA]]s (tRNAs) into the ribosome-mRNA complex, matching the codon in the mRNA to the anti-codon on the tRNA. Each tRNA bears the appropriate [[amino acid]] residue to add to the [[Peptide|polypeptide]] chain being synthesised. As the amino acids get linked into the growing peptide chain, the chain begins folding into the correct conformation. Translation ends with a [[stop codon]] which may be a UAA, UGA, or UAG triplet.{{cn|date=April 2025}}

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 [[chaperone protein]]s to control the form of the product. Some proteins then excise internal segments from their own peptide chains, splicing the free ends that border the gap; in such processes the inside "discarded" sections are called [[intein]]s. Other proteins must be split into multiple sections without splicing. Some polypeptide chains need to be cross-linked, and others must be attached to [[Cofactor (biochemistry)|cofactors]] such as haem (heme) before they become functional.{{cn|date=April 2025}}

== Additional transfers of biological sequential information ==

=== Reverse transcription ===
[[Image:Extended Central Dogma with Enzymes.jpg|right|thumb |550px |Unusual flows of information highlighted in green]]
{{Main|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 [[retrovirus]]es, such as [[HIV]], as well as in [[eukaryote]]s, in the case of [[retrotransposon]]s 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|Reverse Transcriptase]].{{cn|date=April 2025}}

=== RNA replication ===
{{Main|RNA-dependent RNA polymerase}}

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 polymerase]]s, are also found in many eukaryotes where they are involved in [[RNA silencing]].<ref>{{cite journal | vauthors = Ahlquist P | title = RNA-dependent RNA polymerases, viruses, and RNA silencing | journal = Science | volume = 296 | issue = 5571 | pages = 1270–3 | date = May 2002 | pmid = 12016304 | doi = 10.1126/science.1069132 | bibcode = 2002Sci...296.1270A | s2cid = 42526536 }}</ref>

[[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.{{cn|date=April 2025}}

== Activities unrelated to the central dogma ==

The central dogma of molecular biology states that once sequential information has passed from nucleic acid to protein it cannot flow back from protein to nucleic acid. Some people{{Who|date=April 2025}} believe that the following activities conflict with the central dogma.

=== Post-translational modification ===
{{Main|Post-translational modification}}

After protein amino acid sequences have been translated from nucleic acid chains, they can be edited by appropriate enzymes. This is a form of protein affecting protein sequence not protein transferring information to nucleic acid.{{Citation needed|date=April 2025}}

=== Nonribosomal peptide synthesis ===
{{Main|Nonribosomal peptide}}

Some proteins are synthesized by '''nonribosomal peptide synthetases''', which can be big protein complexes, each specializing in synthesizing only one type of peptide. Nonribosomal peptides often have [[cyclic compound|cyclic]] and/or branched structures and can contain non-[[proteinogenic]] [[amino acid]]s - both of these factors differentiate them from ribosome synthesized proteins. An example of nonribosomal peptides are some of the antibiotics.{{Citation needed|date=April 2025}}

=== Inteins ===
{{Main|Intein}}

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 repair#Double-strand breaks|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.{{Citation needed|date=April 2025}}

=== Prions ===
{{Main|Prion}}

[[Prion]]s are proteins of particular amino acid sequences in particular conformations. They propagate themselves in host cells by making [[Protein conformation#Levels of protein structure|conformational changes]] in other molecules of protein with the same amino acid sequence, but with a different conformation that is functionally important or detrimental to the organism. Once the protein has been transconformed to the prion folding it changes function. In turn it can convey information into new cells and reconfigure more functional molecules of that sequence into the alternate prion form. In some types of prion in [[fungi]] this change is continuous and direct; the information flow is Protein&nbsp;→&nbsp;Protein.{{cn|date=April 2025}}

Some scientists such as [[Alain E. Bussard]] and [[Eugene Koonin]] have argued that prion-mediated inheritance violates the central dogma of molecular biology.<ref>{{cite journal | vauthors = Bussard AE | title = A scientific revolution? The prion anomaly may challenge the central dogma of molecular biology | journal = EMBO Reports | volume = 6 | issue = 8 | pages = 691–4 | date = August 2005 | pmid = 16065057 | pmc = 1369155 | doi = 10.1038/sj.embor.7400497 }}</ref><ref>{{cite journal | vauthors = Koonin EV | title = Does the central dogma still stand? | journal = Biology Direct | volume = 7 | pages = 27 | date = August 2012 | pmid = 22913395 | pmc = 3472225 | doi = 10.1186/1745-6150-7-27 | doi-access = free }}</ref> 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."<ref>{{cite book | last = Ridley | first = Rosalind | name-list-style = vanc | date = 2001 | chapter = What Would Thomas Henry Huxley Have Made of Prion Diseases? | editor-first = Harry F. | editor-last = Baker | title = Molecular Pathology of the Prions | url = https://archive.org/details/molecularpatholo00bake_152 | url-access = limited | series = Methods in Molecular Medicine | publisher = Humana Press | pages = [https://archive.org/details/molecularpatholo00bake_152/page/n1 1]–16 | isbn = 0-89603-924-2 }}</ref>

== Use of the term ''dogma'' ==

In his [[autobiography]], ''[[What Mad Pursuit: A Personal View of Scientific Discovery|What Mad Pursuit]]'', Crick wrote about his choice of the word ''[[dogma]]'' and some of the problems it caused him:

<blockquote>
"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."
</blockquote>

Similarly, [[Horace Freeland Judson]] records in ''The Eighth Day of Creation'':<ref>{{cite book |title=The Eighth Day of Creation: Makers of the Revolution in Biology | first = Horace Freeland | last = Judson | name-list-style = vanc | year=1996 | isbn=978-0-87969-477-7 | chapter=Chapter 6: ''My mind was, that a dogma was an idea for which there was ''no reasonable evidence''. You see?!'' |publisher=Cold Spring Harbor Laboratory Press |location=Cold Spring Harbor, NY| edition = 25th anniversary }}</ref>

<blockquote>"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."</blockquote>

== Comparison with the Weismann barrier ==

[[File:Weismann's Germ Plasm.svg|thumb|upright=1.5|In [[August Weismann]]'s [[germ plasm]] theory, the hereditary material, the germ plasm, is confined to the [[gonad]]s. Somatic cells (of the body) [[embryology|develop afresh]] in each generation from the germ plasm. Whatever may happen to those cells does not affect the next generation.]]

The [[Weismann barrier]], proposed by [[August Weismann]] in 1892, distinguishes between the "immortal" germ cell lineages (the [[germ plasm]]) which produce gametes and the "disposable" somatic cells. Hereditary information moves only from [[germline]] cells to [[somatic cells]] (that is, somatic mutations are not inherited). This, before the discovery of the role or structure of DNA, does not predict the central dogma, but does anticipate its gene-centric view of life, albeit in non-molecular terms.<ref>{{cite journal | vauthors = De Tiège A, Tanghe K, Braeckman J, Van de Peer Y |title=From DNA- to NA-centrism and the conditions for gene-centrism revisited |journal=Biology & Philosophy |date=January 2014 |volume=29 |issue=1 |pages=55–69 |doi=10.1007/s10539-013-9393-z |s2cid=85866639 }}</ref><ref>{{cite book | last = Turner | first = J. Scott | editor-last1=Henning | editor-first1 = Brian G.| editor-last2 = Scarfe | editor-first2 = Adam Christian | name-list-style = vanc |title=Biology's Second Law: Homeostasis, Purpose, and Desire |work=Beyond Mechanism: Putting Life Back Into Biology |url=https://books.google.com/books?id=naQm1_Lutq4C&pg=PA192 |year=2013 |publisher=Rowman and Littlefield |isbn=978-0-7391-7436-4 |page=192 |quote=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.}}</ref>

== See also ==
{{Portal|Biology}}
* [[Life]]
* [[Cell (biology)]]
* [[Cell division]]
* [[Gene]]
* [[Gene expression]]
* [[Epigenetics]]
* [[Genome]]
* [[Alternative splicing]]
* [[Genetic code]]
* [[Riboswitch]]{{clear}}

== References ==
{{reflist|32em}}

== Further reading ==
{{refbegin|32em}}
* {{cite journal | vauthors = Bussard AE | title = A scientific revolution? The prion anomaly may challenge the central dogma of molecular biology | journal = EMBO Reports | volume = 6 | issue = 8 | pages = 691–4 | date = August 2005 | pmid = 16065057 | pmc = 1369155 | doi = 10.1038/sj.embor.7400497 }}
* Baker, Harry F. (2001). ''Molecular Pathology of the Prions (Methods in Molecular Medicine)''. Humana Press. {{ISBN |0-89603-924-2}}
* {{cite journal | vauthors = Li JJ, Biggin MD | title = Gene expression. Statistics requantitates the central dogma | journal = Science | volume = 347 | issue = 6226 | pages = 1066–7 | date = March 2015 | pmid = 25745146 | doi = 10.1126/science.aaa8332 | bibcode = 2015Sci...347.1066L | doi-access = free }}
* {{cite journal | vauthors = Piras V, Tomita M, Selvarajoo K | title = Is central dogma a global property of cellular information flow? | journal = Frontiers in Physiology | volume = 3 | pages = 439 | year = 2012 | pmid = 23189060 | pmc = 3505008 | doi = 10.3389/fphys.2012.00439 | doi-access = free }}
* {{cite journal | vauthors = Robinson VL | title = Rethinking the central dogma: noncoding RNAs are biologically relevant | journal = Urologic Oncology | volume = 27 | issue = 3 | pages = 304–6 | year = 2009 | pmid = 19414118 | doi = 10.1016/j.urolonc.2008.11.004 }}
{{refend}}

== External links ==
{{Commons category |Central dogma of molecular biology}}
* [http://www.nature.com/scitable/ebooks/cntNm-16553173 '''The Elaboration of the Central Dogma'''] – ''Scitable: By [[Nature (journal)|Nature]] education''
* [http://naturedocumentaries.org/2149/central-dogma-biology-2008/ Animation of Central Dogma from RIKEN] - NatureDocumentaries.org
* [http://sandwalk.blogspot.co.nz/2007/01/central-dogma-of-molecular-biology.html Discussion on challenges to the "Central Dogma of Molecular Biology"]
* [http://scienceonthesquares.blogspot.com/2012/09/a-primer-for-molecular-biology.html Explanation of the central dogma using a musical analogy]
* [http://embryo.asu.edu/pages/francis-harry-compton-crick-1916-2004 "Francis Harry Compton Crick (1916–2004)" by A. Andrei at the Embryo Project Encyclopedia]

{{Gene expression}}
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[[Category:History of genetics]]
[[Category:Molecular biology]]
[[Category:Molecular genetics]]