The
central dogma of molecular biology was first articulated by
Francis CrickFrancis 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 1958 and re-stated in a
NatureNature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...
paper published in 1970:
- The central dogma of molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
deals with the detailed residue-by-residue transfer of sequential informationInformation in its most restricted technical sense is a message or collection of messages that consists of an ordered sequence of symbols, or it is the meaning that can be interpreted from such a message or collection of messages. Information can be recorded or transmitted. It can be recorded as...
. It states that such information cannot be transferred back from protein to either protein or nucleic acid.
In other words, the process of producing proteins is irreversible: a protein cannot be used to create DNA.
The dogma is a framework for understanding the transfer of
sequenceIn mathematics, a sequence is an ordered list of objects . Like a set, it contains members , and the number of terms is called the length of the sequence. Unlike a set, order matters, and exactly the same elements can appear multiple times at different positions in the sequence...
informationInformation in its most restricted technical sense is a message or collection of messages that consists of an ordered sequence of symbols, or it is the meaning that can be interpreted from such a message or collection of messages. Information can be recorded or transmitted. It can be recorded as...
between sequential information-carrying
biopolymerBiopolymers are polymers produced by living organisms. Since they are polymers, Biopolymers contain monomeric units that are covalently bonded to form larger structures. There are three main classes of biopolymers based on the differing monomeric units used and the structure of the biopolymer formed...
s, in the most common or general case, in living
organismIn biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
s. There are 3 major classes of such biopolymers:
DNADeoxyribonucleic 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...
and
RNARibonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
(both nucleic acids), and
proteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
. 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 specific conditions in case of some viruses or in a laboratory), and 3
unknown transfers (believed never to occur). The general transfers describe the normal flow of biological information: DNA can be copied to DNA (
DNA replicationDNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
), DNA information can be copied into mRNA (
transcriptionTranscription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
), and proteins can be synthesized using the information in mRNA as a template (
translationIn molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
).
Biological sequence information
The
biopolymerBiopolymers are polymers produced by living organisms. Since they are polymers, Biopolymers contain monomeric units that are covalently bonded to form larger structures. There are three main classes of biopolymers based on the differing monomeric units used and the structure of the biopolymer formed...
s DNA, RNA and proteins, are linear polymers (i.e.: each monomer is connected to at most two other monomers). The
sequenceA sequence in biology is the one-dimensional ordering of monomers, covalently linked within in a biopolymer; it is also referred to as the primary structure of the biological macromolecule.-See also:* Protein sequence* DNA sequence...
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 sequence.
General transfers of biological sequential information
Table of the 3 classes of information transfer suggested by the dogma
| General | Special | Unknown |
| DNA → DNA |
RNA → DNA |
protein → DNA |
| DNA → RNA |
RNA → RNA |
protein → RNA |
| RNA → protein |
DNA → protein |
protein → protein |
DNA replication
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 called
helicaseHelicases are a class of enzymes vital to all living organisms. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands using energy derived from ATP hydrolysis.-Function:Many cellular processes Helicases are a...
that unwind the
superhelixA superhelix is a molecular structure in which a helix is itself coiled into a helix. This is significant to both proteins and genetic material, such as overwound circular DNA....
, unwind the double-stranded DNA helix, and, using
DNA polymeraseA DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
and its associated proteins, copy or
replicateDNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
the master template itself so the cycle can repeat DNA → RNA → protein in a new generation of cells or organisms.
Transcription
Transcription is the process by which the information contained in a section of DNA is transferred to a newly assembled piece of
messenger RNAMessenger 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...
(mRNA). It is facilitated by
RNA polymeraseRNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
and
transcription factorIn molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s. In
eukaryoteA eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
cells the primary transcript (
pre-mRNAPrecursor mRNA is an immature single strand of messenger ribonucleic acid . pre-mRNA is synthesized from a DNA template in the cell nucleus by transcription. Pre-mRNA comprises the bulk of heterogeneous nuclear RNA...
) is often processed further via
alternative splicingAlternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
. In this process, blocks of mRNA are cut out and rearranged, to produce different arrangements of the original sequence.
Translation
Eventually, this mature mRNA finds its way to a
ribosomeA ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
, where it is
translatedIn molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
. 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 nucleusIn cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
) is usually separated from the site of translation (the
cytoplasmThe cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within 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
codonsThe genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
, usually beginning with an AUG, or initiator
methionineMethionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
codon downstream of the
ribosomeA ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
binding site. Complexes of
initiation factorInitiation factors are proteins that bind to the small subunit of the ribosome during the initiation of translation, a part of protein biosynthesis.They are divided into three major groups:*Prokaryotic initiation factors*Archaeal initiation factors...
s and
elongation factorElongation factors are a set of proteins that facilitate the events of translational elongation, the steps in protein synthesis from the formation of the first peptide bond to the formation of the last one.Elongation is the most rapid step in translation:...
s bring
aminoacylatedAminoacylation is the process of adding an aminoacyl group to a compound.-See also:*Acylation*tRNA aminoacylation*Transfer RNA-like structures...
transfer RNATransfer 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 (tRNAs) into the ribosome-mRNA complex, matching the codon in the mRNA to the anti-codon in the tRNA, thereby adding the correct
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
in the sequence encoding the gene. As the amino acids are linked into the growing peptide chain, they begin folding into the correct conformation. Translation ends with a UAA, UGA, or UAG stop codon. The nascent polypeptide chain is then 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
inteinAn intein is a segment of a protein that is able to excise itself and rejoin the remaining portions with a peptide bond. Inteins have also been called "protein introns"....
.
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
retrovirusA retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
es, such as
HIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, as well as in
eukaryoteA eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s, in the case of
retrotransposonRetrotransposons are genetic elements that can amplify themselves in a genome and are ubiquitous components of the DNA of many eukaryotic organisms. They are a subclass of transposon. They are particularly abundant in plants, where they are often a principal component of nuclear DNA...
s and
telomereA telomere is a region of repetitive DNA sequences at the end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes. Its name is derived from the Greek nouns telos "end" and merοs "part"...
synthesis.
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 polymeraseRNA-dependent RNA polymerase , , or RNA replicase, is an enzyme that catalyzes the replication of RNA from an RNA template...
s, are also found in many eukaryotes where they are involved in
RNA silencingRNA silencing refers to a family of gene silencing effects by which the expression of one or more genes is downregulated or entirely suppressed by the introduction of an antisense RNA molecule...
.
RNA editingThe term RNA editing describes those molecular processes in which the information content in an RNA molecule is altered through a chemical change in the base makeup. To date, such changes have been observed in tRNA, rRNA, mRNA and microRNA molecules of eukaryotes but not prokaryotes...
, in which an RNA sequence is altered by a complex of proteins and a "guide RNA", could also be considered 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 express proteins from foreign DNA templates, and
neomycinNeomycin is an aminoglycoside antibiotic that is found in many topical medications such as creams, ointments, and eyedrops. The discovery of Neomycin dates back to 1949. It was discovered in the lab of Selman Waksman, who was later awarded the Nobel Prize in Physiology and medicine in 1951...
was found to enhance this effect.
Methylation
Variation in
methylationDNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...
states of DNA can alter
gene expressionGene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
levels significantly. Methylation variation usually occurs through the action of DNA
methylaseA methylase is an enzyme that attaches a methyl group to a molecule.These are found in prokaryotes and eukaryotes. Bacteria use methylase to differentiate between foreign genetic material and their own, thus protecting their DNA from their own immune system...
s. When the change is heritable, it is considered epigenetic. When the change in information status is not heritable, it would be a
somatic epitypeA somatic epitype is a non-heritable epigenetic alteration in a gene. It is similar to conventional epigenetics in that it does not involve changes in the DNA primary sequence...
. The effective information content has been changed by means of the actions of a protein or proteins on DNA, but the primary DNA sequence is not altered.
Prions
PrionA prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...
s 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 happens from one generation to the next, i.e. Protein → Protein. While this represents a transfer of information, prion interactions leave the sequence of the protein unchanged, and so are not technically considered an exception to the central dogma.
Use of the term "dogma"
In his
autobiographyAn autobiography is a book about the life of a person, written by that person.-Origin of the term:...
,
What Mad PursuitWhat Mad Pursuit: A Personal View of Scientific Discovery is a book published in 1988 and written by Francis Crick, the English co-discoverer in 1953 of the structure of DNA, perhaps the greatest discovery ever made in molecular biology...
, Crick wrote about his choice of the word
dogmaDogma is the established belief or doctrine held by a religion, or a particular group or organization. It is authoritative and not to be disputed, doubted, or diverged from, by the practitioners or believers...
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 hypothesisA hypothesis is a proposed explanation for a phenomenon. The term derives from the Greek, ὑποτιθέναι – hypotithenai meaning "to put under" or "to suppose". For a hypothesis to be put forward as a scientific hypothesis, the scientific method requires that one can test it...
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 MonodJacques Lucien Monod was a French biologist who was awarded a Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and Andre Lwoff "for their discoveries concerning genetic control of enzyme and virus synthesis"...
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 JudsonHorace Freeland Judson was a historian of molecular biology and the author of several books, including The Eighth Day of Creation, a history of molecular biology, and The Great Betrayal: Fraud In Science, an examination of the deliberate manipulation of scientific data.-Life and career:The Eighth...
records in
The Eighth Day of Creation:
"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."
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