Deoxyribonucleic acid (English: deoxyribonucleic acid, abbreviated as DNA), also known as deoxyribonucleic acid, is a molecule that can form genetic instructions and guide biological development and life function operation. Its main function is long-term information storage, which can be compared to "blueprint" or "menu". The instructions contained therein require the construction of other compounds in cells, such as protein and RNA. DNA fragments with genetic information are called genes and other DNA sequences, some of which directly work with their own structures, while others participate in regulating the expression of genetic information.
DNA double helix DNA is a long-chain polymer, its constituent unit is called nucleotide, and sugar and phosphoric acid molecules are connected through ester bonds to form its long-chain skeleton. Each sugar molecule is connected with one of the four bases, and the sequence formed by these bases arranged along the long chain of DNA can form a genetic code, which is the basis of protein's amino acid sequence synthesis. The process of reading the password is called transcription, which is to copy a nucleic acid molecule called RNA according to the DNA sequence. Most RNA carries the information of synthesizing protein, while others have their own special functions, such as rRNA, snRNA and siRNA.
In cells, DNA can be organized into chromosome structure, and the whole set of chromosomes is collectively called genome. Chromosomes replicate before cell division, a process called DNA replication. For eukaryotes, such as animals, plants and fungi, chromosomes are stored in the nucleus; For prokaryotes, such as bacteria, they are stored in nucleoid substances in cytoplasm. Chromatin proteins on chromosomes, such as histoproteins, can organize and compress DNA and help it interact with other protein, thus regulating gene transcription.
The earliest sketch of DNA double helix drawn by Francis Harry Compton Crick in history. See: History of Molecular Biology.
Friedrich Michel is a Swiss doctor. He was the first person to isolate DNA. 1869, he found some substances that can only be observed by a microscope from the pus left in the abandoned bandage. Because these substances are in nuclides, Michelle called them "nuclides". By 19 19, Febbas Levin further determined the nucleotide units of bases, sugars and phosphates that make up DNA. He thinks that DNA may be composed of many nucleotides connected in series through phosphate groups. But in his concept, a long DNA chain is short, and the bases in it are arranged repeatedly in a fixed order. 1937, Astbury William Thomas completed the first X-ray diffraction pattern, which clarified the regularity of DNA structure.
1928, Frederick Griffith discovered from Griffith's experiment that the smooth pneumococcus can be transformed into the rough type of the same bacteria by mixing the dead smooth type and the rough type. This phenomenon is called "transformation". But the factor that caused this phenomenon, namely DNA, was not recognized by Oswald Avery until 1943. 1953, Alfred Hirsch and Martha Cowles Chase confirmed the genetic function of DNA. They found in Hirsch Chase's experiment that DNA is the genetic material of T2 phage.
Painted windows commemorating Crick and DNA structure at Cambridge University.
1953, james watson and Francis Harry Compton Crick of Cavendish Laboratory put forward the earliest accurate model of DNA structure based on the X-ray diffraction pattern taken by rosalind franklin of King's College London and related materials, and published it in Nature. Five experimental evidence papers about this model were also published in Nature on the same topic. Among them are papers by Franklin and Raymond Gosling. The X-ray diffraction pattern attached in this paper is the key evidence for Watson and Crick to clarify the structure of DNA. In addition, maurice wilkins's team is also one of the publishers of papers in the same period. Franklin and Gosling then put forward the difference between the double helix structure of type A and type B DNA. 1962, Watson, Crick and Wilkins won the Nobel Prize in Physiology or Medicine.
In a speech from 65438 to 0957, Crick put forward the central principle of molecular biology, predicted the relationship between DNA, RNA and protein, and expounded the "transposon hypothesis" (later called tRNA). 1958, Matthew Mei Sen Starr and Franklin Starr confirmed the mechanism of DNA replication in Starr experiment in Mei Sen. Later, Crick's team's research showed that the genetic code consists of three bases in a non-repetitive way, called codons. Hal Gobin Corana, Dr Robert W. Holley and marshall warren nirenberg finally solved the genetic code composed of these codons. In order to detect all human DNA sequences, the Human Genome Project was launched in190' s, and by 200 1, the international team with transnational cooperation and the private company Celera Genome Company published the draft human genome sequence in Nature and Science respectively.
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Physical and chemical properties DNA fragment structure animation, various bases horizontally arranged between two spiral long chains. Zoom in
Two long DNA chains will intertwine with each other in a right-handed way to form a double helix structure. Because the phosphate-linked skeleton is located on the outside, there will be some gaps between the two chains, so even from the outside of the helix, the bases located inside the helix can still be seen (as shown in the animation on the right). There are two kinds of grooves (or "grooves") on the surface of the double helix: the larger one is 22 angstroms wide; The smaller width is 12 angstrom. Because the side of each base near the big groove is easy to contact with the outside world, protein usually acts on the side near the big groove when contacting with the base, and protein can bind to specific sequences, such as transcription factors.
The interaction between DNA and tissue protein (white part above), a basic amino acid in protein (blue at the bottom left), can combine with acidic phosphate group on DNA (red at the bottom right).
Structural proteins can bind to DNA, which is a common example of non-specific DNA protein interaction. Structural proteins in chromosomes combine with DNA to form a complex, which makes DNA organize into a compact chromatin structure. For eukaryotes, chromatin is composed of DNA and a small basic protein called histidine. This structure in prokaryotes is doped with many types of protein. Double-stranded DNA can be attached to the surface of tissue protein and wound twice to form a discoid complex called nucleosome. Ionic bonds can be formed between the basic residues in tissue protein and the acidic glycophosphate skeleton on DNA, which makes them interact nonspecific and separates the base sequences in the complex. Chemical modification of basic amino acid residues, including methylation, phosphorylation and acetylation, can change the intensity of interaction between DNA and tissue proteins, thus changing the difficulty of contacting DNA with transcription factors and affecting the transcription rate. Other nonspecific DNA binding proteins located in chromosomes also include a highly mobile histone, which can preferentially bind DNA and deform it. This kind of protein can change the arrangement of nucleosome and produce more complex chromatin structure.
There is a class of DNA-binding proteins that specifically bind to single-stranded DNA, called single-stranded DNA-binding proteins. Human replication protein A is one of the most studied proteins. It acts on most processes related to double helix melting, including DNA replication, recombination and DNA repair. This binding protein can immobilize single-stranded DNA and make it more stable, thus avoiding the formation of stem loops or hydrolysis due to nuclease.
λ repressor is a kind of transcription factor with spiral structure, which can bind to DNA target.
On the contrary, other protein can only specifically bind to specific DNA sequences. Most of the research on this kind of protein focuses on various transcription factors that can regulate transcription. Each of these protein can bind to a specific DNA sequence, thereby activating or inhibiting gene transcription of the sequence located near the promoter. Transcription factors can function in two ways. The first one can bind to RNA polymerase responsible for transcription directly or through other intermediate proteins, and then the polymerase binds to the promoter to start transcription. The second one binds to the enzyme that specially modifies tissue protein on the promoter, which changes the difficulty of contacting DNA template with polymerase.
Because the target DNA may be scattered in the whole genome of an organism, changing the activity of a transcription factor may affect the operation of many genes. Therefore, these transcription factors often become the target of signal transmission, that is, as a medium for cells to reflect environmental changes or differentiation and development. Specific transcription factors will interact with DNA, creating many contact points around DNA bases, so that other protein can "read" these DNA sequences. Most of the base interactions occur in the sulcus, which is the most accessible site for bases from the outside.
The restriction enzyme EcoRV (green) forms a complex with its receptor DNA.
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3. 1 DNA modifying enzyme?
Nuclease and ligase
Nuclease is an enzyme that cleaves DNA chains by catalyzing the hydrolysis of phosphodiester bonds. One of them is called nucleic acid exonuclease, which can hydrolyze nucleotides located at the end of DNA long chain; The other is endonuclease, which acts on the position between the two endpoints of DNA. Restriction endonuclease is the most commonly used nuclease in the field of molecular biology, which can cut specific DNA sequences. For example, EcoRV in the left picture can recognize the 6-base 5'GAT | ATC 3' sequence and cut it off from the position where the vertical line between GAT and atc is located. This enzyme can digest phage DNA in nature to protect bacteria infected by phage, which is part of the restrictive modification system. Technically, nucleases with sequence specificity can be applied to molecular cloning and DNA fingerprinting.
Another enzyme, DNA ligase, can use the energy of adenosine triphosphate or nicotinamide adenine dinucleotide to reconnect the broken DNA long chain. Ligase is especially important for the delayed chain produced during DNA replication. These short fragments located in replication fork can be glued into a complete copy of DNA template under the action of this enzyme. In addition, ligase is also involved in DNA repair and gene recombination.
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Topoisomerase and helicase
Topoisomerase is an enzyme with both nuclease and ligase functions, which can change the supercohelicity of DNA. Some of them first cut one strand of the DNA double helix to form a gap, so that the other strand can pass through the gap, thus reducing the degree of super helix, and finally combine the cut parts. The other is to cut two DNA strands at the same time, let the other double-stranded DNA pass through this gap, and then the gap is bonded. Topoisomerase is involved in many DNA-related functions, such as DNA replication and transcription.
Helicase is a kind of molecular motor, which can break the hydrogen bond between bases by using chemical energy from various nucleoside triphosphates, especially adenosine triphosphate, and untie DNA double helix into single strand. This enzyme is involved in most DNA-related functions, and it must be in contact with bases to play its role.
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polymerase
Polymerase is an enzyme that uses nucleoside triphosphate to synthesize polyglycoside chains. This method connects one nucleotide to the 3' hydroxyl position of another nucleotide, so all polymerases are synthesized in the direction of 5' to 3'. At the activation position of this kind of enzyme, nucleoside triphosphate receptor will base pair with the template of single-stranded polyglycoside, so that polymerase can accurately synthesize another complementary polyglycoside chain according to the template. Polymerase can be classified according to the types of available templates.
In the process of DNA replication, DNA polymerase can synthesize a copy of DNA sequence by means of DNA template. Because the accuracy of this replication process is necessary for life support, many of these polymerases have the function of correction, which can identify accidental configuration errors in synthetic reactions, that is, some bases that cannot be paired with another strand. When an error is detected, the exonuclease activity of the nucleic acid in the direction of 3' to 5' will take effect and the wrong base will be removed. In most organisms, DNA polymerase acts as a large complex called replicon, which contains many extra subunits, such as DNA fragments or helicase.
DNA polymerase, which relies on RNA as a template, is a special polymerase, which can copy long-chain RNA sequences into DNA versions. Among them, a viral enzyme called reverse transcriptase is involved in the infection process of retrovirus to cells; In addition, there is telomerase needed to replicate telomeres, and its structure contains RNA templates.
Transcription is carried out by RNA polymerase that relies on DNA as a template for synthesis. This enzyme can copy the sequence on the long chain of DNA into RNA version. In order to start gene transcription, RNA polymerase will first combine with a DNA sequence called a promoter to separate the two strands of DNA, and then copy the gene sequence into messenger RNA until it reaches a terminator sequence that can end transcription. Just like DNA polymerase which depends on DNA template in human body, RNA polymerase II, which is responsible for the transcription of most genes in human genome, is also a part of large protein complex, which is subject to multiple regulation and contains many additional subunits.
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4. Cross structure produced in the process of gene recombination. The red, blue, green and yellow in the picture represent four different DNA long chains. See also: gene recombination.
In the process of recombination, two chromosomes (M and F) break and then recombine to produce two rearranged chromosomes (C 1 and C2).
The interaction between DNA helices does not often occur. Every chromosome in the human nucleus has a region called "chromosome field". Physical separation between chromosomes is very important for maintaining the stability of DNA information storage function.
However, sometimes recombination occurs between chromosomes. In the process of recombination, chromosome exchange will occur: first, two DNA helices will break, then exchange their fragments and finally recombine. Recombination makes chromosomes exchange genetic information and produce new gene combinations, thus increasing the effect of natural selection, and may have an important impact on the evolution of protein. Gene recombination is also involved in DNA repair, especially when DNA breaks in cells.
Homologous recombination is the most common way of chromosome exchange, which can occur on two chromosomes with similar sequences. On the other hand, nonhomologous recombination is harmful to cells, causing chromosome translocation and genetic abnormality. Enzymes that can catalyze recombination reactions, such as RAD5 1, are called "recombinases". The first step of recombination is endonuclease action, or DNA double strand breaks caused by DNA damage. The recombinant enzyme can catalyze a series of steps to combine two helices to produce Holiday hybridization. Among them, the single-stranded DNA in each helix is connected with the complementary DNA on the other helix, thus forming a cross-shaped structure, which can move within the chromosome and lead to the exchange of DNA strands. The recombination reaction will eventually stop because of the breakage of the cross structure and the re-adhesion of DNA.
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5 evolution of DNA biological metabolism The genetic information contained in DNA is the basis of all modern life functions, and it is also the basis of the growth and reproduction of organisms. However, in the 4 billion years of life history, it is not clear when DNA appeared and began to work. Some scientists think that early life forms may be based on RNA as genetic material. RNA may play a major role in early cell metabolism, on the one hand, it can transmit genetic information; On the other hand, it can also be catalyzed as a part of ribozyme. In the ancient RNA world, nucleic acids have both catalytic and genetic functions, and these molecules may later evolve into the current genetic code form consisting of four nucleotides, because the fewer types of bases, the higher the accuracy of replication; When there are more kinds of bases, the catalytic efficiency of nucleic acid increases. Two kinds of functions that can achieve different purposes finally reach the optimal number in the case of four bases.
However, there is no direct evidence about this ancient genetic system, and because DNA cannot survive in the environment for more than one million years, it will gradually degrade into short fragments in solution, so there is no DNA in most fossils for research. Even so, some people claim to have obtained older DNA. A study said that DNA had been isolated from bacteria living in salt crystals 250 million years ago, but this announcement caused discussion and controversy.
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6 technology application?
6. 1 genetic engineering See also: molecular biology and genetic engineering.
Recombinant DNA technology is widely used in modern biology and biochemistry. The so-called recombinant DNA refers to artificial DNA assembled from other DNA sequences, which can transform DNA into biological individuals by carrying plasmids or virus vectors in the required format. After genetic modification, organisms can be used to produce recombinant proteins for medical research or agricultural cultivation.
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6.2 See: Genetic Fingerprint Analysis for forensic identification.
Forensic doctors can use DNA in blood, skin, saliva or hair left over from the crime scene to identify possible criminals. This process is called genetic fingerprinting or DNA characterization. This analysis method compares the lengths of many repeated DNA fragments in different human individuals, including short tandem repeats and microsatellite sequences, and is usually the most reliable criminal identification technology. However, if the crime scene is contaminated by many people's DNA, it will become more complicated. 1984 The first person to develop DNA characterization was British geneticist Alec Jeffreys. 1988, British murder suspect Colin Pitchfork became the first person to be convicted for DNA qualitative evidence. Using the DNA samples of specific criminals, a database can be established to help investigators solve some old cases that only collect DNA samples from the scene. In addition, DNA identification can also be used to identify victims in major disasters.
6.3 History and Anthropology See: phylogeny and genetic genealogy.
Because DNA will accumulate some genetic mutations after a period of time, the historical information contained in it can enable geneticists to understand the evolutionary history of organisms as species by comparing DNA sequences. These studies are a part of phylogeny and a useful tool of evolutionary biology. If DNA sequences within species are compared, then population geneticists can know the history of a specific population. The application of this method can range from ecological genetics to anthropology. For example, DNA evidence has been used to find ten missing tribes in Israel. DNA can also be used to investigate the kinship of modern families, such as building the family relationship between Sally Hemings and Thomas Jefferson's descendants. The research method is quite similar to the above-mentioned criminal investigation, so sometimes some criminal investigation cases can be solved because the DNA of the crime scene matches the DNA of the criminal's relatives.
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6.4 Bioinformatics See Bioinformatics.
Bioinformatics has influenced the application, search and data mining of DNA sequence data, and developed various technologies for storing and searching DNA sequences, which can be further applied to computer science, especially string search algorithm, machine learning and database theory. String search or comparison algorithm is to find the occurrence position of a single sequence or several letters from larger sequences or more letters, which can be developed into searching for specific nucleotide sequences. In other applications, such as text editors, simple algorithms can usually be used to solve problems, but only a small number of DNA sequences with recognizable characteristics cause these algorithms to run poorly. Sequence alignment attempts to identify homologous sequences and locate specific mutation positions that make these sequences different. Multiplex sequence alignment technique can be used to study the functions of germline * * * and protein. The data of the whole genome contains a large number of DNA sequences, such as the research object of the human genome project. It will be quite difficult to mark the position of each gene on each chromosome and the gene responsible for regulation. Gene recognition algorithm can identify the regions with protein or RNA coding characteristics in DNA sequence, so that researchers can predict the special gene products that may be expressed in organisms before experiments.
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6.5 DNA and computer See: DNA manipulation.
The earliest application of DNA in operational research is to solve a small direct Hamilton path problem that belongs to NP-complete. DNA can be used as "software" to write information into nucleotide sequences; And use enzymes or other molecules as "hardware" to read or modify. For example, FokI, as a hardware restriction enzyme, can carry a piece of GGATG sequence DNA with software function, then input it together with other DNA fragments, react with the software-hardware complex, and finally output another piece of DNA. This Turing-like device can be used for drug therapy. In addition, DNA operation is superior to electronic computer in energy consumption, space requirement and efficiency, and DNA operation is a highly parallel calculation method (see parallel operation). Many other problems, including the simulation of various abstract machines, Boolean satisfiability problem and bounded traveling salesman problem, have been analyzed by using DNA operations. Because of its compactness, DNA has also become a part of cryptography theory, especially because it can effectively construct and use an unbreakable one-time codebook.
The DNA nanostructure produced by self-assembly on the left is a computer diagram, and you can see the four intersections of DNA double helix. On the right is the image measured by atomic force microscope.
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6.6 DNA and nanotechnology See Synonyms at DNA and nanotechnology
The molecular characteristics of DNA, such as self-assembly, enable it to be used in some nano-scale construction techniques, such as using DNA as a template to guide the growth of semiconductor crystals. Or use DNA itself to make some special structures, such as DNA "tiles" or polyhedrons formed by crossing long chains of DNA. In addition, some movable elements can be made, such as nano-mechanical switches, which can change the configuration by transforming DNA between different optical isomers (B-type and Z-type), thus causing the switch to be turned on or off. There is also a DNA machine with a structure similar to tweezers, which can add foreign DNA to open and close tweezers and discharge waste DNA. At this time, DNA is like "fuel" Devices constructed from DNA can also be used as the above-mentioned DNA computing tools.
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7 see hereditary diseases
dna sequencing
Nanbuluo
dna microarray
From a macro point of view, teaching methods can be divided into: teaching methods to obtain indirect experience in the form of language, teaching