Central rule

The central dogma of molecular biology

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Central Dogma molecular biology The central dogma of molecular biology (English: Francis Crick It was proposed in 1958 and reiterated in an article in Nature 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 from protein to either protein or nucleic acid. （ molecular biology The central principle of is to specify the word for word transmission of serial information. It states that genetic information Cannot be controlled by protein Transfer to protein or nucleic acid Middle.)

It refers to genetic information from DNA Pass to RNA , and then from RNA Pass to protein , that is, complete genetic information Of Transcription and translate Process. It can also be accessed from DNA Pass to DNA , that is, complete DNA Replication process for. This is all there are Cellular structure The laws that our creatures follow. In some viruses RNA Self replication (e.g Tobacco mosaic virus And can use RNA as template in some viruses Reverse transcription become DNA The process (some carcinogenic viruses) is a supplement to the central rule.

The central law is often misunderstood, especially with genetic information "By DNA reach RNA reach protein ”Is confused with the standard process. Some information flows different from the standard process are mistaken as exceptions to the central rule. In fact Prion Is the only known exception to the central rule.

The standard process of genetic information can be roughly described as follows: "DNA makes RNA, RNA makes protein, and protein in turn assists the first two processes and helps DNA self replicate".

Richard Pomerantz The team's paper published in Scientific Progress in June 2021 is the first to prove that RNA can also be written back to DNA, which challenges the core principles of biology.^[8]

Chinese name: Central rule
Foreign name: genetic central dogma
And translated into: molecular biology The central dogma of

Proposer: Francis Crick
Proposed time: 1958
primary coverage: Complete the process of transcription and translation of genetic information

catalog

seven Gene coding
eight General transmission of genetic information
▪ Transcription
▪ edit
▪ Splicing
▪ translate
▪ DNA replication
▪ Viruses with RNA genomes only
▪ Pseudoretrotranscript

nine Special transmission of genetic information
▪ Reverse transcription
▪ RNA replication
▪ Catalytic function of RNA
▪ Direct synthesis of proteins using DNA as template
▪ DNA also has enzyme activity
ten Extension of central rule
▪ Post translation modification
▪ Intron of protein

▪ DNA methylation
▪ Protein can be used as a template for DNA synthesis
▪ Prion
eleven The origin of the central law
▪ Evolution from RNA to DNA
▪ Evidence for splicing DNA with mRNA
twelve RNA is written back to DNA

brief introduction

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genetic information Intracellular Biomacromolecule The basic principle of inter transfer. Included in Deoxyribonucleic acid（ DNA) or Ribonucleic acid（ The functional nucleotide sequence in RNA) molecule is called genetic information 。 The transfer of genetic information includes the transfer between nucleic acid molecules, nucleic acid and protein molecules.

1957 F. H.C. Crick The central rule initially proposed is: DNA → RNA → Protein. It shows that the transfer of genetic information between different macromolecules is one-way, irreversible, and can only be from DNA to RNA（ Transcription ）, from RNA to protein（ translate ）。 These two forms of information transfer have been confirmed in all biological cells. 1970 H M. Temin and D. Baltimore found in some RNA carcinogenic viruses that their replication process in host cells is to synthesize a DNA molecule And then synthesize new viral RNA using DNA molecule as template. The previous step is called Reverse transcription Is a new discovery after the above central rule was proposed. therefore Crick In 1970, he reiterated the importance of the central rule and proposed a more complete graphical form.

here genetic information The first type is represented by solid arrows, including DNA replication, RNA transcription and protein translation, that is, ① DNA → DNA (replication); ② DNA → RNA (transcription); ③ RNA → protein (translation). These three genetic information The direction of metastasis commonly exists in all biological cells. The second type, represented by dotted arrows, is the transfer of genetic information under special circumstances, including RNA replication, RNA reverse transcription to DNA and direct translation from DNA to protein. Namely ① RNA → RNA (replication); ② RNA→DNA（ Reverse transcription ）；③ DNA → protein. RNA replication Only in RNA virus Exists in. Reverse transcription was first found in RNA oncoviruses, and later in human white blood cell And placental trophoblast Transcriptase Activity. as for genetic information Direct transfer from DNA to protein is only theoretically possible and has not been found in living cells.

Crick It is considered that the information transfer without arrow in the diagram is impossible, that is, ① protein → protein; ② Protein → RNA; ③ Protein → DNA. The central argument of the central rule is: genetic information Once transferred to protein molecules, they can neither be transferred from protein molecules to protein molecules nor reversed from protein molecules to nucleic acid molecules. Crick It is believed that this is because the molecular structures of nucleic acid and protein are completely different, and the information transfer between nucleic acid molecules is through Watson Crick type Base pairing And implement. However, the transfer of information from nucleic acid to protein requires an extremely complex translation mechanism in existing biological cells, which cannot perform reverse translation. Therefore, if it is necessary to transfer genetic information from protein to nucleic acid, there should be another set of reverse translation mechanism in the cell, which does not exist in existing cells. The central rule reasonably explains the two types of cell life activities macromolecule The function of nucleic acid is to store and transfer genetic information, guide and control protein synthesis; The main function of protein is to carry out metabolic activities and act as Cellular structure Components of.

neutron activation analysis

RNA self replication and Reverse transcription The process cannot be carried out when the virus exists alone, and only occurs when it parasitizes in the host cell. Reverse transcriptase It is very important in genetic engineering enzyme , which can take known mRNA as Template synthesis Target gene 。 It is an important means to obtain target genes in genetic engineering.

Using DNA as a template to synthesize RNA is the main way of RNA synthesis in the biological world. But some organisms, like some viruses, store their genetic information in RNA molecules. When they enter the host cell, they pass on by replication. They synthesize RNA molecules under the catalysis of RNA guided RNA polymerase. When using RNA templates, they synthesize complementary RNA molecules in the direction of 5 '→ 3' under the action of RNA replicase, However, the RNA replicase lacks the correction function, so the error rate of RNA replication is high, which is similar to the characteristics of reverse transcriptase.^[1]

Discovery Overview

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RNA Transcription 1

As early as 1909, A. E. Garrod described Melanuria Genes and Urine melanate oxidase Relationship. Originated from Breadfruit rubrum (Streptospora) Biochemical genetics G · W · Beadle, 1941, and Tatum (E · L · Tatum) put forward the hypothesis of "one gene and one enzyme" together, believing that genes act through enzymes.

gene (DNA) located primarily in the nucleus. If the enzyme (chemical essence is protein) is synthesized in the nucleus, the problem is simple, and the gene directly guides the enzyme synthesis. But this is not the case.

As early as the 1940s, J. Hammerling and J. Brachet found that Cymbidium and Sea urchin Egg cell After removing the nucleus, it can still be used for a period of time protein synthesis 。 This indicates that the cytoplasm can carry out protein synthesis. In 1955, Littlefield and 1959, K. McQuillen respectively used mice and Escherichia coli To prove that ribosome in cytoplasm is the site of protein synthesis. In this way, the DNA in the nucleus must pass the genetic information to the cytoplasm through a "message".

RNA Transcription 2

In 1955, Brazier onion Root tip and Amoeba Experiment for materials, he uses Ribonuclease (RNA enzyme) breaks down the ribonucleic acid (RNA) in the cell, and the synthesis of protein stops. If the yeast extract is added RNA The protein synthesis will be restored to a certain extent. In the same year, Goldstein and Plaut observed the transfer of radiolabeled RNA from the nucleus to the cytoplasm. Therefore, people speculate that RNA is a messenger between DNA and protein synthesis. In 1961, F. Jacob and mono (J. Monod) formally proposed the term and concept of "messenger ribonucleic acid" (mRNA). In 1964, C. Marbaix from the rabbit Reticulocyte A kind of molecular weight Large and short-lived RNA is considered as mRNA.)

In fact, as early as 1947, French scientists A. Boivin and R. Vendrell《 experiment 》A joint paper was published in the journal to discuss the possible information transmission relationship between DNA, RNA and protein. An unknown editor understood the central idea of this paper as that DNA makes RNA, and then RNA makes protein. Ten years later, in September 1957, Crick A paper entitled "On Protein Synthesis" was submitted to the Society for Experimental Biology and published on page 138, volume 12 of the Society for Experimental Biology. This paper was evaluated as“ genetics One of the most enlightening and emancipating works in the field. " In this paper, Crick It was formally proposed that the transmission direction of genetic information flow is DNA → RNA → protein, which was later called the "central rule" by scholars.

The principle of biological genetic center was first proposed by Crick in 1958 to indicate the flow direction or transmission law of life genetic information. Because at that time Transcription , translation Genetic code 、 Peptide chain We didn't know much about folding and so on. At that time, the central rule had certain hypothetical properties. With the further exploration of biological genetic law, the central law has been gradually improved and confirmed.^[2]

History

① In 1965, scientists found that RNA can be replicated;

② In 1970, scientists discovered reverse transcriptase;

③ In 1982, scientists found that Mad cow disease It is a disease caused by a protein with abnormal structure.

content

① From DNA to DNA (DNA self replication);

② From DNA to RNA, and then to protein (transcription and translation);

③ From RNA to RNA (RNA self replication);

④ From RNA to DNA (reverse transcription)

Note: The first two are the main embodiment of the central law, and the last two are the perfection and supplement of the central law.

effect

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Central law is one of the most important and basic laws in modern biology. It has played a huge role in exploring the essence and universal laws of life phenomena, greatly promoted the development of modern biology, is the theoretical cornerstone of modern biology, and points out the direction for the unification of basic theories of biology, and plays an important role in the development of biological science.^[3] genetic material It can be DNA or RNA. The genetic material of cells is DNA, while that of some viruses is RNA. This virus with RNA as its genetic material is called Retrovirus（ retrovirus）， During the infection cycle of this virus, single stranded RNA molecules Reverse transcriptase（ Reverse transcriptase) can be reverse transcribed into single stranded DNA, and then use single stranded DNA as template to generate double stranded DNA. Double stranded DNA can become host cell Part of the genome, and passed to Daughter cell 。 Under the catalysis of reverse transcriptase, RNA molecules produce DNA molecules complementary to their sequences. This DNA molecule is called complementary DNA, abbreviated as cDNA. This process is called reverse Transcription（ reverse transcription）。

significance

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thus it can be seen, genetic information It is not necessarily a one-way flow from DNA to RNA, and the genetic information carried by RNA can also flow to DNA. However, the genetic information contained in DNA and RNA only flows unidirectionally to protein, and so far, it has not been found that the information of protein flows inversely to nucleic acid. The flow direction of this genetic information is Crick The genetic significance of the generalized central law.

Any hypothesis must be tested by scientific facts. Reverse transcriptase The discovery of makes the central rule modify the one-way flow of genetic information from DNA to RNA. Genetic information can flow between DNA and RNA. Then, whether the information flow between DNA, RNA and protein molecules is only one-way flow from nucleic acid to protein molecules, or whether the information of protein molecules can also flow to nucleic acid, the central rule still affirms the former. However, pathogens Prion (Prion)'s behavior once posed a serious challenge to the central law.^[4]

gene expression

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relationship

Gene directed protein synthesis; Gene controlled organism; Biological traits are directly reflected by proteins.

Regulation method

a. Genes control the metabolic process by controlling the synthesis of enzymes, and then control the biological characteristics;

b. Genes control protein synthesis protein structure And then directly control the characteristics of organisms.

Prion

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Prion is a kind of protein infectious particle, which was initially recognized as the pathogen of sheep pruritus. It's chronic Nervous system diseases It was discovered more than 200 years ago. In 1935, French researchers found that the disease could be transmitted in sheep through vaccination, which means that this pathogen is an infectious factor that can replicate itself in host objects. Prions are also human central nervous system Degenerative diseases such as Kuru disease (Kuru) and Creutzfeldt Jacobdisease (CJD) can also cause Mad cow disease That is, bovine spongiform encephalopathy (BSE). Later studies have proved that this prion is not a virus, but a protein particle without nucleic acid. A protein molecule that does not contain DNA or RNA can host cell It generates the same molecule as itself and realizes the same biological function, that is, it causes the same disease, which means that this protein molecule is also loaded and transmitted genetic information Substances. This fundamentally shook the foundation of genetics.^[5]

Experiments have proved that prions are indeed protein particles without DNA and RNA, but they are not carriers of genetic information, nor can they Self replication However, it is still an isomer of a normal protein produced by gene coding.

Gene coding

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Mammalian cell The gene in the produces a glycoprotein PrP. Human PrP gene is located in the short arm of chromosome 20, and there are 253 PrP genes amino acid It is a signal peptide composed of 22 amino acids at the amino terminal. PrP in normal brain tissue is called PrPc, relative molecular mass 33 000~35 000, right protease sensitive. PrP in the diseased brain tissue is called PrPsc, with a relative molecular weight of 27 000~30 000. It is a part of PrPc, and protease has no effect on it. PrPc and PrPsc are two isomers of PrP. The amino acid composition and linear order are the same, but the three-dimensional conformation is different. PrPc structure. Spiral accounted for 42%, and β lamella accounted for 30%; PrPsc is. Helix accounted for 30%, and beta lamella accounted for 43%. 4 items of PrPc. Helixes can be arranged into a compact spherical structure, and the stochastic fluctuation of this structure will grow into a partially folded monomer PrP *, which is an intermediate, that is, PrP * can generate both PrPc and PrPsc. Generally, the content of PrP * is very small, so the generated PrPsc is very small. However, exogenous PrPsc can make PrP * become PrPsc. The insolubility of PrPsc makes the formation of PrPsc irreversible. PrPsc accumulates in a large amount in nerve cells, causing pathological changes in nerve cells and destroying the function of nerve cells. Therefore, after PrPsc infects normal cells, it can promote the production of more PrPsc in cells, and PrPsc gradually accumulates, which requires a time process to cause disease, which is the reason why this neurodegenerative disease has a long latency. So PrPsc enters host cell Instead of self replicating, PrPc generated by gene coding in cells is transformed into PrPsc. It can be seen that the central law is correct, or at least needs no correction.

General transmission of genetic information

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The Central Rule is a framework for understanding the transmission order of genetic information between biological macromolecules. There are nine possible transmission orders for three main types of biological macromolecules in organisms: DNA, RNA and protein. The rule divides these sequences into three categories, three general transfers (usually in most cells), three special transfers (can occur, but only under certain conditions), and three unknown transfers (may not occur).

Transmission order of three types of genetic information in the rule
commonly	special	unknown
DNA → DNA	RNA → DNA	Protein → DNA
DNA → RNA	RNA → RNA	Protein → RNA
RNA → protein	DNA → Protein	Protein → Protein

Transcription

Main entry: Transcription

Transcription is the process of transforming genetic information from DNA to RNA. Transcription is Messenger RNA (mRNA) and Non coding RNA (tRNA, rRNA, etc.). During transcription, a gene will be read and copied into mRNA; This process is controlled by RNA polymerase (RNA polymerase) and transcription factor (translation factor).

edit

Main entry: RNA editing

RNA editing refers to the process of changing genetic information at the RNA level, resulting in mismatch between mature RNA coding sequence and its transcription template DNA sequence. RNA editing has been found in tRNA, rRNA and mRNA of eukaryotes. RNA editing includes nucleotide deletion or insertion editing and base replacement editing. This change affects gene expression, generates different amino acids and new Open code reading frame 。 Editing can be regulated at various levels and has certain relevance to some human diseases.

Splicing

Main entry: Splicing

stay Eukaryotic cell The original transcripts (mRNA precursors) are also processed: one or more sequences（ Intron ）It is cut out and removed. Alternative splicing The mechanism of Exon 。 Not all living cells with mRNA undergo this splicing; Splicing does not exist in prokaryotic cells.

translate

Main entry: Translation (Genetics)

Eventually, mature mRNA approaches the ribosome and is translated here. Prokaryotic cells have no nucleus, and their transcription and translation can be carried out simultaneously. In eukaryotic cells, the transcription site and the translation site are usually separate (the former is in the nucleus, and the latter is in the cytoplasm), so mRNA must be transferred from the nucleus to the cytoplasm, and combine with the ribosome in the cytoplasm. Ribose can be expressed by three Codon To read the information on mRNA, usually starting from AUG, or ribosome Start downstream of connection position methionine The codon begins. Inception factor and Elongation factor The compound of Aminoacyl tRNA (tRNAs) are introduced into the ribosome mRNA complex. As long as the codon on the mRNA can pair with the anti codon on the tRNA, they can be added according to the code sequence on the mRNA amino acid 。 When one amino acid is linked into a peptide chain, it will start to fold into the correct configuration. This folding process will continue until the original polypeptide chain is released from the ribosome and forms a mature protein. In some cases, newly synthesized polypeptide chains need additional treatment to become mature proteins. The correct folding process is quite complex, and may require another process called Molecular chaperone Help. Sometimes the protein itself will be further cut. At this time, the "abandoned" part inside is called Endoceptide 。

DNA replication

Main entry: DNA replication

As the last step of the central rule, DNA must be faithfully copied to transfer the genetic code from parents to offspring. Replication is completed by a group of complex proteins; These proteins open Superhelix Structure DNA double helix Structure and utilize DNA Polymerase And its related proteins, copy or duplicate the original template, so that the new generation of cells or the body can repeat DNA → RNA → protein The cycle of. DNA molecule has configuration diversity. In the process of transmission and expression of genetic information, DNA conformation has the transformation process from left-handed helix and right-handed helix to right-handed helix, so it should have the transformation form of nucleic acid conformation.

Viruses with RNA genomes only

Some viruses contain a complete set of RNA encoded genome Therefore, they only have RNA → protein compiled form.

Pseudoretrotranscript

Main entry: Pseudoretrotranscript

Found in plants in recent years Retrovirus The genetic material of this virus is double stranded DNA. Like retroviruses, it can replicate by integrating its DNA into the host genome DNA.

Special transmission of genetic information

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Reverse transcription

Main entry: Reverse transcription

After the central law was elaborated, people found that Retrovirus 。 These viruses can be transmitted through a method called Reverse transcriptase RNA is used as a template to reverse transcribe cDNA and then transcribe RNA from cDNA. This confirmed the existence of RNA to DNA transcription. It was initially thought that this phenomenon only appeared in viruses, but recently, RNA to DNA transcription was also found in higher animals Retrotransposon 。

RNA replication

Main entry: RNA replication

The genetic material of some viruses is RNA molecule, which is propagated by RNA replication and uses RNA as a template RNA replicase Catalyzed synthesis of RNA molecules, RNA replicase lacks correction function, and has a high error rate during replication. RNA replicase only acts on the RNA of the virus itself, not on the RNA molecules in the host cell.

Catalytic function of RNA

Main entry: RNA catalysis

It has always been thought that all kinds of biochemical reactions in organisms are catalyzed by enzymes, while RNA only stores and transmits information, and has nothing to do with enzyme catalytic reactions. Ribonuclease P Is a kind of ribozyme , that is, by a RNA Molecules play a catalytic role. It is the first discovered protein with catalytic activity Biomacromolecule 。 Its function is to cut tRNA The superfluous sequence of RNA or precursor in the molecule. RNA can directly express some genetic information of itself without protein, and this information is not encoded by the triplet code of nucleotide.

Direct synthesis of proteins using DNA as template

It was observed in some in vitro experiments that Protein synthesis inhibitor antibiotics as neomycin and streptomycin , which can disrupt the selection of messengers by ribosomes and thus be acceptable Single strand DNA molecule Instead of mRNA, it is then translated into amino acid sequence of polypeptide according to nucleotide sequence using single strand DNA as template. In addition, studies have shown that DNA in the nucleus can be transferred directly to the ribosome in the cytoplasm, and protein synthesis can be controlled without RNA.

DNA also has enzyme activity

In 1994, G.F. Joyce and others found that a synthetic DNA molecule has a special phosphodiesterase Activity. Since then, many cases have reported that synthetic DNA sequences have different enzyme activities. In 1995, Chinese scholar Wang Shengli and others found that DNA extracted from various organisms had esterase activity and could catalyze the hydrolysis of naphthalene acetate to naphthol and acetic acid. This weak esterase activity is a general property of non-specific DNA and does not require specific sequence of DNA coding.

Extension of central rule

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Crick In the above 1970 article, it was pointed out that although the central rule is useful for guiding experiments, it should not be taken as a dogma:

"Although the various principles proposed in this paper seem reliable, our understanding of molecular biology, even if it is just a cell - let alone the whole life in nature - is still far from complete, enough for us to take it as a dogma and affirm its correctness"

——Crick

Since Crick published his article in 1970, many new discoveries have demonstrated the necessity of supplementing and developing the central rule.

Post translation modification

Main entry: Post translation modification

For most proteins, this is the final step in protein biosynthesis. Post translational modifications of proteins can attach other biochemical functional groups, change the chemical properties of amino acids, or cause structural changes to expand the function of proteins. Enzymes can remove amino acids from the N-terminal end of a protein or cut peptide chains from the middle. For example, insulin is the hormone of peptide. It will be cut twice after the establishment of double sulfur bond, and the precursor of polypeptide will be removed in the middle of the chain. The formed protein contains two polypeptide chains connected by double sulfur bond. Other modifications, like phosphorylation, are part of the mechanism that controls protein activity. Protein activity can be to activate or inactivate enzymes.

Intron of protein

Main entry: Protein intron

Protein has self splicing phenomenon, which is the same as mRNA. Some protein precursors have Intron (intein) sequence, some regions in the middle of the polypeptide sequence are processed and removed, and the rest of the protein Exon (extern) reconnects to protein molecules.

DNA methylation

Main entry: Epigenetics

Epigenetics studies reversible and heritable changes in gene function without changes in nuclear DNA sequence. These changes include DNA modification (such as methylation) RNA interference Various modifications of histones. It also refers to the study of the procedures involved in biological development. In both cases, the research object includes the problem of how to transfer gene regulation information not included in DNA sequence to the next generation (cell or organism). The main research contents include two aspects. One is the regulation of gene selective transcriptional expression, including DNA methylation, gene imprinting, histone covalent modification, and chromatin remodeling. The other is post transcriptional regulation of genes, including non coding RNA, microRNA, antisense RNA, intron and riboswitch in the genome.

Main entry: DNA methylation

DNA methylation is a form of DNA chemical modification, which can change the genetic performance without changing the DNA sequence. It is part of epigenetic code and is an epigenetic mechanism. The process of DNA methylation will add methyl groups to DNA molecules, for example, on the 5 'carbon of cytosine ring: this 5' direction of DNA methylation can be seen in all vertebrates.

Protein can be used as a template for DNA synthesis

From Mount Researchers at Sinai Hospital have found a new type called Rev1 DNA Polymerase It can provide coding information for DNA replication. Many carcinogens tend to destroy the guanine (G) of DNA or the pairing of guanine and cytosine (C), which will lead to DNA mismatch. The newly discovered protein can use itself as a template to add a cytosine to the replication chain. This cytosine will be added by Rev1 regardless of whether guanine exists in the DNA chain. A single strand can be used in DNA replication according to Base pairing principle Replicate new DNA strands. Cells use this new mechanism to replicate damaged DNA in the presence of carcinogens. This is the first time that protein can be used as a template for DNA synthesis.

Prion

Main entry: Prion

Prions are a class of proteins that replicate themselves precisely by changing the conformation of other proteins. That is: protein → protein. This infectious factor is mainly composed of proteins. The infectious factor Prp is slightly different from the normal factor PrP in shape. Scientists speculate that this deformed protein will cause normal PrP to change into infectious protein, and this chain reaction will make normal protein and pathogenic protein factors become new viruses.

The origin of the central law

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The information of the central rule is from DNA to RNA, but Xie Ping (2014) pointed out that Origin of life From the perspective of evolution history, the integration of information must be from mRNA to DNA^[6] 。

Evolution from RNA to DNA

stay Cell origin In order to adapt to the cell division behavior, genetic material Therefore, the integration of genetic information stored in various m-RNAs in cells must become the direction of selection. Connecting all m-RNA information is the start of the development in the direction of DNA. It may be thought that with the increase of protein, mRNA also increases correspondingly. Occasionally, an integrated mRNA long chain better matches the cell's division behavior, so it will be selected.

However, not splicing m-RNA together is DNA. In fact, two changes have taken place in the structural components Uracil In DNA Thymine , although there is only a slight difference between the two, that is, the latter has an extra methyl; Second, the Ribose In DNA Deoxyribose 。 But these two changes lead to two nucleic acid Significant differences in morphology: DNA forms a double helix structure, while most RNA molecules are linear single strands, although some regions of RNA molecules can fold back to complement and pair bases, forming a local double helix. Perhaps for some structural reason, if deoxyribose replaces ribose and thymine replaces uracil, it will be more conducive to the formation of stable Double helix structure In other words, that is the directionality of DNA selection.

Of course, perhaps just to avoid confusion, because organisms often use structural materials that are both connected and differentiated to perform different functions, for example, NADPH and NADH They have the same reduction potential and similar function, but they are used in different biological metabolic pathways. An orderly metabolic system that is not easily confused will certainly be selected or favored^[6] 。

Evidence for splicing DNA with mRNA

Eukaryotic gene The transcript is Monocistron That is, one gene encodes one Polypeptide chain Or RNA chain, each gene transcription has its own Regulating element 。 stay Prokaryotic cell Medium, usually several different mRNA Connected together, they are separated from each other by a short interval sequence that does not code for proteins. This mRNA is called Polycistron mRNA 。 In my opinion, prokaryotes Polycistron The existence of RNA can be regarded as the evidence of a transitional stage of mRNA splicing of long strand DNA.

dna replication

Another proof is that DNA Polymerase Before copying a new DNA strand according to the template, it must rely on a RNA primer 。 This primer is Primer enzyme A short RNA strand that is composed in the direction of 5 'to 3' after recognizing the starting site and uncoiling a piece of DNA. After that, DNA Polymerase Will pass Phosphodiester bond 's connection, adding with Template chain Matched nucleotides to synthesize DNA towards the 3 'end of the primer chain. Finally, of course, RNA hydrolase（ RNase ）Will RNA primer Hydrolysis, other DNA polymerase will generate DNA to fill these gaps.

ATP Center Hypothesis on the Origin of Genetic Coding System^[7]

It can be imagined that if the genetic information of m-RNA is not integrated into a unified DNA, cell division It is hard to imagine how to accurately distribute the pro cells into two sub cells! Recently Xie Ping (2015) proposed that heredity Codon It is part of the biochemical system, and the core of the biochemical system is ATP It is ATP that establishes the connection between nucleic acid and protein（ ATP center hypothesis ）^[7] 。

Of course, the establishment of a perfect genetic system is by no means easy, which is beyond human imagination. It should be the evolution of cell precursors over hundreds of millions of years, especially in the process of numerous failed divisions. People may doubt the truth of this inference, but in such a grand earth, in such a small cell, if given a billion years of time, all accidents may become inevitable, and all unimaginable events may occur, as long as there is a direction of evolution.

The differentiation and improvement of protein, RNA and DNA in structure and function has led to the formation of a completely independent genetic system, which in turn is through cell division Maintain life form relative stability The premise of. Only with the emergence of a truly operable genetic system can life move from the pre cellular era to the cellular era, and then it really opens up Biological evolution The prologue of.

In terms of biochemical mechanism, cells must form a structural system with both differences and connections, that is, on the one hand, they must information Accurate storage and replication, on the other hand, efficient implementation of life construction, the former is the nucleic acid system, the latter is the protein system. The two systems are relatively independent on a short time scale, but they constantly interact, resulting in Coevolution^[6] 。

RNA is written back to DNA

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Associate Professor of Biochemistry and Molecular Biology, Thomas Jefferson University Richard Pomerantz The team's paper published in Scientific Progress in June 2021 is the first to prove that RNA can also be written back to DNA, which challenges the core principles of biology.^[8]

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