Nucleic acid is a kind of organismpolymer, an essential component of all known life forms, is the most important substance in all biological molecules, widely exists in all animal and plant cellsmicroorganismIn vivo.
Nucleic acid consists of nucleotides, while nucleotide monomer consists ofPentose, phosphate group andNitrogenous baseform.If five carbon sugar isRibose, the polymer formed is RNA;If five carbon sugar isDeoxyribose, the polymer formed is DNA.
Nucleotide is the basic unit of nucleic acid, that is, the monomer of nucleic acid molecule.A nucleotide molecule is composed of a nitrogenous base, a moleculePentoseAnd one moleculephosphoric acidComposed of.Nucleic acids can be divided intoDeoxyribonucleic acid(DNA) andRibonucleic acid(RNA).
nucleic acid
DNA
RNA
name
Deoxyribonucleic acid
Ribonucleic acid
structure
Regular double helix structure
Usually in single chain structure
Basic unit
Deoxyribonucleotide
Ribonucleotide
Pentose
Deoxyribose
Ribose
Nitrogenous base
A (adenine)
G (Guanine)
C (cytosine)
T (thymine)
A (adenine)
G (Guanine)
C (cytosine)
U (Uracil)
distribution
It mainly exists in the nucleus, and a small amount exists in mitochondria and chloroplasts
It mainly exists in the cytoplasm
function
Carrying genetic information, it plays an extremely important role in the heredity, variation and protein biosynthesis of organisms
As genetic material: only in RNA viruses;Not as genetic material: It plays a role in the process of DNA controlling protein synthesis.MRNA is a direct template for protein synthesis, tRNA can carry specific amino acids, and rRNA is a component of ribosome;Catalysis: a kind of enzyme
Nucleic acid analogue
Nucleic acid analogueIt is a compound similar to the naturally occurring RNA and DNA (similar in structure), used for medical and molecular biological research.Nucleic acid analogues have changed between the nucleotides that make up nucleic acids and the bases, pentose and phosphate groups that make up nucleotides[1]。Generally, these changes change the base pairing and base stacking properties of nucleic acid like species.For example, universal bases can pair with all four classic bases, and phosphate sugar skeleton analogs (such as PNA) can even form triple helix[2]。Nucleic acid analogues, also known as heteronucleotides, represent one of the main pillars of heterobiology, that is, life design based on alternative biochemistry and new natural forms.
Nucleic acid analogues includePeptide nucleic acid(PNA), morpholino and locked nucleic acids (LNA), and glycol nucleic acids (GNA) andThreonucleic acid（TNA）。Because the main chains of molecules have changed, they are obviously different from natural DNA or RNA.
effect
DNA is stored, copied and transmittedgenetic informationThe main material basis of.
In addition, many other kinds of functional RNAs are known, such as microRNAs.
Nucleic acid analogues are mainly used in medical and molecular biology research[1-2]。
history
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Discovery of nucleic acids
Nucleic acid was first introduced by Swiss doctors and biologists in 1869Frederick MichelIt is obtained by separation and is called Nuclein[3]。
In the early 1980s, German biochemist, winner of the 1910 Nobel Prize in Physiology and MedicineKosselThe nucleic acid was further purified and its strong acidity was found.He also later identified the nuclear base.
In 1889, German pathologist Richard Altmann created the term nucleic acid[4], replacing Nuclein.
In 1919, an American Russian doctor and chemistPhoebe LevinFirst, the sequence of the three main components (phosphate, pentose and nitrogen) of single nucleotide was found.[5]
In 1938, British physicist and biologistWilliam Astbury And Florence Bell (later renamed Florence Sawyer) published the first X-ray diffraction pattern of DNA[6]。
American molecular biologist in 1953James Watson And British molecular biologistsFrancis Crick Identified the structure of DNA[7]。
The experimental research of nucleic acids constitutes an important part of modern biology and medical research, and lays the foundation for genomics, forensic science, biotechnology and pharmaceutical industry.
Molecular size and composition
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Molecular size
Nucleic acid molecules are usually very large.actually,DNA moleculeIt may be the largest single biomolecule known.
But there are also relatively small nucleic acid molecules.
Nucleic acid molecules range in size from 21 nucleotides（Small interfering RNA）ToMacrochromosome(The human chromosome is a single molecule containing 247 million base pairs[8]）Not equal.
chemical composition
Nucleic acid is completely hydrolyzed to produce alkaline substances such as purine and pyrimidine, a mixture of pentose (ribose or deoxyribose) and phosphoric acid.Partial hydrolysis of nucleic acid produces nucleic acid and nucleotide.Each nucleoside molecule contains a molecule of base and a molecule of pentose, and a molecule of nucleotide is partially hydrolyzed to produce nucleoside as well as a molecule of phosphoric acid.
DNA and RNA contain different ribose. DNA contains deoxyribose, while RNA contains ribose.In addition, DNA and RNA contain different bases: both DNA and RNA contain adenine, cytosine and guanine, but DNA does not contain uracil, onlyThymine
The sugar and phosphate in nucleic acid pass throughPhosphodiester bondThey are linked by alternating chains (sugar phosphate skeletons).The carbon connected by the phosphate group is the 3 '- terminal of the sugar, and the carbon bound to the carbon atom is the 5' - terminal, which produces the directionality of nucleic acids.Nucleotides are linked to sugars through N-glycosidic bonds.
Non standard nucleosides are also found in RNA and DNA, and they usually come from the modification of standard nucleosides or initial RNA transcripts in DNA molecules.Transfer RNA (tRNA) molecules contain particularly many modified nucleosides.
Molecular composition
Natural DNA molecules are double stranded in most cases, while RNA molecules are single stranded[9]。However, there are many exceptions.Some viruses haveDouble stranded RNAConstitute the genome, while othersVirusesHas a single stranded DNA genome[10]In some cases, the nucleic acid structure with three or four chains can be formed[11]。
Relevant nature
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chemical property
Acid effect: Nucleic acid is completely hydrolyzed into base, ribose or deoxyribose and phosphoric acid under strong acid and high temperature.At slightly dilute concentrationInorganic acidMedium, most easily hydrolyzedChemical bondcoverselectivityThe cleavage of, usually connecting purine and riboseGlycosidic bondTo produce purine free nucleic acid.
Alkali effect: When the pH value exceeds the physiological range (pH7-8), it will have a more subtle impact on the DNA structure.The base effect changes the tautomeric structure of the base.This change affects the hydrogen bonding between specific bases, resulting in the dissociation of DNA double strands, which is called DNA denaturation.At high pH, the same denaturation occurs in the helical region of RNA, but is usually masked by alkaline hydrolysis of RNA.
Chemical denaturation: Some chemicals can denature DNA or RNA at neutral pH.If the energy stability of the secondary structure of nucleic acid formed by the stacked hydrophobic base is weakened, the nucleic acid will denature.
physical property
Viscosity: The high axial ratio of DNA and other properties make its aqueous solution highly viscous. Long DNA molecules are easy to be damaged by mechanical force or ultrasound, and the viscosity decreases.
Buoyancy density: It can be purified and analyzed according to the density of DNA.At high concentrations of molecular weightSalt solutionIn (CsCl), the density of DNA is roughly the same as that of the solution. If the solution is centrifuged at high speed, CsCl tends to settle at the bottom, thus establishingdensity gradientAnd DNA finally settles on itBuoyancy densityThe corresponding position forms a narrow band, and this technology becomes a balanceDensity gradient centrifugationorIsodensity gradient centrifugation。
Stability: The structure of nucleic acid is quite stable, which is mainly due to the hydrogen bond between base pairs, the accumulation of bases and cations in the environment.
Spectroscopic properties
Hypochromism:dsDNAbe relative tossDNAIt is subtractive, while ssDNA is hyperchromic relative to dsDNA.
DNA purity: judged by measuring A260/A280 and A260/A230.
Denaturation, renaturation and hybridization
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denaturation
Under the action of certain physical and chemical factors, the hydrogen bond between bases in the nucleic acid double helix and other spatial structures breaks and becomes a single chain phenomenon is calleddenaturation（denaturation）。
Common physical and chemical factors causing nucleic acid denaturation include heating, acid, alkaliureaandFormamideEtc.During denaturation, the spatial conformation of nucleic acid is destroyed and its physical and chemical properties are changed.Due to the exposure of the base inside the double helix molecule, its A260 value will greatly increase.The increase of A260 value is proportional to the degree of chain breaking, which is calledHyperchromic effect（hyperchromic effect）。If the DNA solution is heated slowly and its A260 value is measured at different temperatures, the "S" shaped DNA melting curve can be obtained.It can be seen from the DNA melting curveDNA denaturationThe action is completed in a rather narrow temperature.
When A260 starts to rise, the DNA isDouble helix structure, part of the molecule in the rising regionBase pairIt starts to break, and its value increases with the increase of temperature. There are still a few base pairs in the flat initial part of the upper part to keep the two chains together. This state is maintained until the critical temperature. At this time, the last base pair of DNA molecule is broken, and the two complementary chains are completely separated.Usually, the temperature when the DNA solution A260 rises to half of the maximum value during heating denaturation is called the temperature of the DNAMelting temperature(melting temperature Tm), Tm is a very useful parameter for studying nucleic acid denaturation.Tm is generally between 85 and 95 ℃,Tm valueIt is proportional to the content of G C in DNA molecule.
Renaturation
Under appropriate conditions, denatured DNA can make two separate single strands to form double helix DNA again, which is calledRenaturation（renaturation）。WhenThermal denaturationAfter slow cooling, the DNA ofannealing（annealing）。DNA renaturationIt is a very complex process, and there are many factors affecting the speed of DNA renaturation: high DNA concentration, fast renaturation;DNA molecular renaturation is slow;High temperature can denature DNA, while low temperature can make the mismatch unable to be separated, etc.The best renaturation temperature is Tm minus 25 ℃, generally about 60 ℃.ionic strengthGenerally above 0.4mol/L.
hybridization
Single strand nucleic acid molecules from different sources with complementary sequences, according toBase pairing principleTogether, it is calledNucleic acid hybridization（hybridization）。Hybridization can occur between DNA DNA, RNA RNA and DNA RNA.Hybridization is one of the commonly used techniques in molecular biology research. It can be used to analyze the structure, location andgene expressionThe commonly used hybridization methods are Southern blotting,Northern blottingandIn situ hybridizationEtc.
scientific research
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On the evening of May 10, 2023, the Tianzhou VI cargo spaceship launched 98 scientific experimental products, including four scientific experiments in the field of space life science and biotechnology, including the research on the molecular evolution of the co origin of protein and nucleic acid and the origin of codons, which will be carried out in the biotechnology experiment cabinet of the Quest Module。[12]
