gene

[jī yīn]

All nucleotide sequences that produce a polypeptide chain or functional RNA

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Genes（ Genetic factor ）Is to produce a Polypeptide chain Or function RNA All you need nucleotide sequence 。 Genes support the basic structure and performance of life. Stored with life race 、 blood type 、 inoculation 、 grow 、 Apoptosis All information of the process. The interdependence of environment and heredity deduces the life Reproduction 、 cell division and protein synthesis And other important physiological processes. The birth, growth, decline, disease, aging, death and other life phenomena of organisms are all related to genes. It is also an internal factor that determines life and health. Therefore, genes have dual attributes: Materiality (mode of existence) and information (fundamental attribute).

have genetic information DNA fragments of are called genes. Other DNA sequences, some of which play a role directly by their own structure, and some are involved in regulating the expression of genetic information. A simple life requires at least 265 to 350 genes. (This involves the power of gene working group, human gene working group and Drosophila melanogaster Are basically similar)

Chinese name: gene
Foreign name: Gene
Role: Record and transmit genetic information

Applied discipline: Cell Biology 、 genetics 、 molecular biology
Characteristics: Stability, development and variability of decisive characters
Propose: 1909 Danish scholar Johnson
Carrier: chromosome

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stay Gregor Mendel Previously, people thought that heredity was a mixed process, but Mendel confirmed that there was an indivisible and independent Genetic unit Later, it was proved that this genetic unit existed in chromosome DNA sequence. Mendel It reveals the genetic process of sexual reproduction at the gene level (called“ Separation law ”And "free combination" law), although he did not know the true existence form of genes at that time^[1] 。 Note that genes and DNA are completely different concepts.

Genetic history

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Genes are the basis for controlling biological traits Genetic unit 。

dna

Austrian geneticist in the 1860s Gregor Mendel It is proposed that the biological characteristics are determined by Genetic factor Control, but this is just a logical reasoning 。 In the early 20th century, geneticists Morgan adopt Drosophila melanogaster And realized that genes exist in chromosome It is linear arrangement on the chromosome, so it is concluded that the chromosome is Gene vector Conclusion. 1909 Denmark geneticist Johnson (W. Johansen, 1859-1927) formally proposed the concept of "gene" in the book "Principles of Precision Genetics".

Since the 1950s, with molecular genetics Development, especially Watson and Crick Propose DNA double helix After structure, people further understand the essence of genes, that is, genes have genetic effect DNA fragments. The results also show that each chromosome Only 1-2 DNA molecule Each DNA molecule has multiple genes, and each gene contains hundreds of thousands Deoxynucleotide 。 since RNA After the discovery of viruses, genes exist not only in DNA, but also in RNA On. Because of different genes Deoxyribonucleotide Order of（ Base Sequence), so different genes contain different genetic information 。 1994 Chinese Academy of Sciences Zeng Bangzhe propose Systematic genetics Concept and principle, explore the gene logic and language of cat and tiger, and propose the relationship between genes and genome Research on the occurrence of logical structure and its programmed expression.

Gene classification

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Structural gene

Coding in gene RNA Or protein base sequence.

(1) Prokaryotic structural genes: continuous, RNA synthesis does not require splicing;

(2) Eukaryotic structural genes: Exon (coding sequence) and Intron (Non coding sequence) consists of two parts.

Nonstructural gene

A non coding DNA segment (i.e. flanking sequence) on both sides of the structural gene, which is involved in gene expression Regulation 。

（1） Cis acting element : can affect gene expression , but does not encode the DNA sequence of RNA and protein;

These include:

Promoter: RNA polymerase Specific recognition of DNA sequences that bind and initiate transcription. It is directional and located upstream of the transcription start site.

Upstream promoter elements: some specific DNA sequences upstream of the TATA box, Trans acting factor It can combine with these elements to regulate the transcription efficiency of genes.

Response element: a specific DNA sequence that binds to activated information molecule receptors and can regulate gene expression.

Enhancer: It combines with trans acting factors to enhance transcriptional activity. It is effective at any position of the gene and has no directionality.

Silencers: negative regulatory elements of gene expression, which combine with trans acting factors to inhibit transcriptional activity.

Poly (A) tailing signal: the conserved AAUAAA sequence at the end of the structural gene and the downstream GT or T rich region are Polyadenylation Specific factor recognition, adding about 200 A at the 3 'end of mRNA.

(2) Trans acting factor: a class of proteins or RNA 。^[2]

Genetic characteristics

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Genes have two characteristics: one is that they can faithfully copy themselves to maintain the basic characteristics of biology; Second, in reproduction, genes can "mutate" and mutate. When the fertilized egg or mother is affected by environment or heredity, harmful defects or mutations will occur in the genome of offspring. The vast majority of diseases occur, and some will be inherited under specific circumstances. Also called genetic disease. Under normal conditions, life will change on the basis of heredity. These changes are normal changes.

Containing specific genetic information nucleotide Sequence, yes genetic material The smallest functional unit of. In addition to the genes of some viruses Ribonucleic acid In addition to RNA, the genes of most organisms are composed of Deoxyribonucleic acid (DNA) and chromosome It is arranged in a linear way. The term gene usually refers to chromosome genes. stay Eukaryote The chromosome is in the nucleus, so it is also called Nuclear gene 。 be located mitochondrion and chloroplast The genes in isoorganelles are called extrachromosomal genes , extranuclear genes or cytoplasmic genes, which can also be called mitochondrial genes plasmid And chloroplast genes.

Gene replication and expression

In general diploid In cells or individuals that can maintain gametes or gamete The lowest set of chromosomes with normal body function is called Chromosome Or genome, a genome contains a whole set of genes. Corresponding All Cytoplasmic gene Constitute a Cytoplasmic genome , which includes Mitochondrial genome and Chloroplast genome Etc. prokaryote The genome of is a simple DNA or RNA molecule, so it is also called Gene band , also known as its chromosome.

The position of a gene on a chromosome is called a locus, and each gene has its own specific locus. stay Homologous chromosome Upper occupation Same seat Of Different forms The genes of Allele 。 In natural populations, there is often a dominant (and therefore often considered normal) allele called wild type Gene; Other alleles at the same locus are generally directly or indirectly generated by mutations of wild-type genes. Compared with wild-type genes, they are called mutant gene 。 There are two in diploid cells or individuals Homologous chromosome So there are two alleles in each locus. If these two alleles are the same, then this Gene locus This kind of cell or individual is called Homozygote ； If the two alleles are different, they are called Heterozygote 。 In a heterozygote, two different alleles often express the trait of only one gene, which is called Dominant gene Another gene is called Recessive gene 。 In diploid biological populations, there are often more than two alleles, and more than two alleles are called Multiple allele 。 However, some genes that were considered to belong to multiple alleles in the early stage are actually not true alleles, but several genes closely related in function and adjacent in position, so they are also called Pseudoallele 。 The existence of some multiple alleles with little difference in phenotypic effects is easy to be ignored, and several alleles in wild populations can be identified through special genetic analysis. This multiple allelic gene that is difficult to distinguish from characters is called Allele 。 Many encodings isozyme The gene of is also an allele.

Genes belonging to the same chromosome form a Linkage group (See Interlocking and switching ）。 The position of genes on chromosomes generally does not reflect their properties and relationships in physiological functions, but their position and arrangement are not completely random. Coding the same in bacteria biosynthesis A series of genes related to enzymes in the pathway are often arranged together to form an operon (see gene regulation ）； In person Drosophila melanogaster and mice In different organisms, it often happens that several genes related to the function are arranged together to form a Gene complex or gene cluster Or called a Pseudoallele Series or complex genes.

Cognitive process

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from Mendel's law People's understanding of genes has been deepening for more than 100 years.

In 1866, the Austrian scholar G J. Mendel used capital letters A and B to represent dominant character Such as round grain, cotyledon yellow, etc., represented by lowercase letters a, b, etc Recessive trait Such as wrinkled grains, green cotyledons, etc. He did not strictly distinguish between the observed traits and the genetic factors controlling them. But judging from the hybridization results he used these symbols to represent genes, they are still used to represent genes in genetic analysis for convenience.

The law of separation of genes

After Mendel's work was rediscovered in the early 20th century, his laws were verified in many animals and plants. 1909 Denmark Scholar W 50. Johnson put forward the term gene, which refers to the genetic factors that control any trait in any kind of organism and whose genetic law conforms to Mendel's law genotype and phenotype The former is the gene component of an organism, and the latter is the trait expressed by these genes.

1910 American geneticist and embryo Scientist T H. Morgan White eye (W) found in Drosophila melanogaster Mutant First, it shows that the gene can mutate, and from this we can know that the wild type gene W+has the physiological function of making the compound eye of drosophila develop into red. In 1911, Morgan was again in the X Linkage gene In the second generation of hybrids of white eye and short wing strains, white eye, short wing Drosophila melanogaster and normal red eye long wing Drosophila melanogaster were found. First, it was pointed out that two genes located on the same chromosome could be located on two homologous chromosomes through chromosome exchange. Exchange is a universal phenomenon Genetic phenomenon However, until the mid-1940s, it was never found that the exchange occurred within a gene. Therefore, at that time, it was believed that a gene was a functional unit, a mutation unit and an exchange unit.

Before the 1940s, the chemical nature of genes was not understood. Until 1944, O T. Avery et al confirmed Diplococcus pneumoniae It is the first time to use experiments to prove that genes are DNA fragments with genetic effects.

1955, used by S. Benze Escherichia coli T4 bacteriophage As material to study rapid lysozyme Mutant R Ⅱ gene fine structure It is found that mutations can occur at many sites within a gene, and exchanges can occur between these sites, which indicates that a gene is a functional unit, but not a mutation unit and exchange unit, because a gene can include many mutation units（ Mutant ）And many restructured units（ Recombinant ）(See Complementarity ）。

In 1969, J. Shapiro et al Lactose operon And make it transcribe in vitro, which proves that a gene can function independently from the chromosome, so the genetic concept of graininess is more established. With the development of recombinant DNA technology and nucleic acid sequence analysis technology, new developments have taken place in the understanding of genes, mainly the discovery of overlapping genes, broken genes and genes that can move.

Overlapping gene

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Schematic diagram of overlapping genes

Overlapping gene It was discovered in 1977. As early as 1913, A H. Stevient It has been proved in drosophila that genes are arranged linearly on chromosomes fine structure Concordance Position effect The results of other studies also show that genes are arranged one after another on chromosomes without overlapping. But in 1977, F. Sanger was determining phage Total DNA of Φ X174 nucleotide sequence However, it was unexpectedly found that gene D contained gene E. The first gene E Codon (See Genetic code ）Starting from the middle of a codon TAT in the center of gene D, the two partially overlapping genes encode two proteins with different sizes and amino acids. In some cases Eukaryote Overlapping genes were also found in the virus.

The broken gene was also found in 1977. It is a gene that contains one or several segments that do not appear in mature mRNA. These fragments that do not appear in mature mRNA are called Intron , the fragments appearing in mature mRNA are called Exon 。 For example, the following gene has three exons and two introns. In several ways mammal Nuclear genes Yeast Broken genes have been found in the mitochondrial genes of. The function of introns and the post transcriptional processing mechanism is an attractive topic in eukaryotic molecular genetics.

Up to now, no less than 1000 genes have been found in Drosophila melanogaster in terms of function, category and number, and about 1000 genes have been located in Escherichia coli. Although the traits determined by genes are different, the original functions of many genes are basically the same.

1945 G. W. Biddle By Neurospora The research of, proposed a gene and an enzyme hypothesis, thought that the original function of genes is determined Primary structure of protein (i.e. coding composition Peptide chain Amino acid sequence). This assumption was fully verified in the 1950s.

Classification

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In the early 1960s, F. Jacob and J. Mono discovered Regulatory gene 。 Differentiate genes into Structural gene And regulatory genes focus on the role of the proteins encoded by these genes: Enzyme protein 、 hemoglobin 、 collagen protein or Crystallin The genes of other proteins are called structural genes; Any code repressing or activating structure Gene transcription The genes of the protein are called regulatory genes. But from the perspective of the original function of genes, they are all coding proteins. Genes can be divided into:

Figure 1

① Genes that encode proteins.

② Genes without translation products.

③ Non transcribed DNA segments.

The action time of each gene in an organism is often different. Some genes are transcribed before replication, which is called Early gene ； Some genes are transcribed after replication, called Late gene 。 A gene mutation that changes several seemingly unrelated traits at the same time is called Pleiotropic gene 。

Basis of different number of organisms factor There are great differences between orders. It has been confirmed that there are only three genes in RNA phage MS2, while there are at least one million genes in each cell of mammals. But most of them are Repeating sequence In non repetitive sequences, the number of genes encoding peptide chain is estimated to be less than 100000. Except for simple Duplicate gene In addition, there are a large number of genes with similar structure and function, which are often closely linked, forming the so-called Gene complex Or called gene family.

Allele: A gene that is located at the same position of a pair of homologous chromosomes and controls different forms of a trait. Different alleles produce such as hair color or blood type And other genetic characteristics. Allelic control Relative character The alleles can be divided into different categories by the apparent recessive relationship and genetic effects of the alleles. In individuals, one form of allele (dominant) can be expressed more than other forms (recessive). Allele is another "version" of the same gene. For example, there is more than one "version" of the gene that controls tongue rolling, which explains why some people can roll their tongues while others cannot. Defective gene versions are associated with certain diseases, such as Cystic fibrosis 。 It is worth noting that each chromosome has a pair of "copies", one from the father and one from the mother. In this way, each of our approximately 30000 genes has two copies. The two copies may be the same (allele) or different. Figure 1 shows a pair of chromosomes, with genes shown in different colors. stay cell division In the process, the appearance of chromosomes is like this. If you compare the gene bands at the same position on two chromosomes (male and female), you will see that some gene bands are the same, indicating that the two alleles are the same; However, some gene bands are different, indicating that the two "versions" (i.e. alleles) are different.

Pseudoallele （pseudoalleles）

Genes with similar phenotypic effects, closely related functions, and closely linked positions on chromosomes. They seem to be alleles, but they are not.

The traditional concept of gene is more complicated due to the discovery of pseudo allele phenomenon. morgan In their early discovery, the school was particularly surprised that the adjacent genes generally seemed to be functionally unrelated to each other and went their own way. Genes that affect eye color, formation of wing veins, formation of bristles, body immunity, etc. may all be adjacent to each other. "Genes" with very similar effects are generally only alleles of a single gene. If genes are exchange units, recombination between alleles will never occur. In fact, Morgan's students failed to find the allele exchange at the white eye gene locus in the early stage (1913; 1916). Later they learned that the main reason was that there were few test samples. However, since Stefan (1925) proposed the rod eye Gene duplication The theory of unequal exchange and Bridges (1936) According to the evidence provided by the salivary gland chromosome to support this theory, the time is ripe to try to recombine between seemingly alleles again. Oliver (1940) was the first to achieve success diamond Evidence of unequal allele exchange was found at the gene locus. Two different alleles (Izg/Izp) are Marker gene The heterozygotes that were put together reverted to the wild type with a frequency of about 0.2%. The recombination of marker genes proved that there was an exchange of "alleles".

The exchange between very close genes can only be observed in an extremely large number of test samples. Since their normal behavior seems to be allelic, they are called Pseudoallele （Lewis，967）。 They are not only functionally similar to true alleles, but also can produce mutant phenotypes after transposition. They not only exist in fruit flies, but also have been found in maize, especially in some microorganisms. Molecular genetics has had many explanations for this problem, however, due to the Gene regulation I don't know much about it, so I can't fully understand it.

The discovery of location effect has had a profound impact. theodosius dobzhansky In a critical article, the following conclusions were made: "A chromosome is not only a mechanical polymer of genes, but also a unit of higher structural levels... The nature of a chromosome is determined by the nature of the gene as its structural unit; However, chromosome is a harmonic system, which not only reflects the history of biology, but also is a decisive factor in this history "(Dobzhaansky, 1936:382).

Some people are not satisfied with this gentle revision of the "beading concept" of genes. since Mendelism There have been some since the beginning biologist (For example, Riddle and Chiid) cited evidence that seems to be of sufficient weight to oppose the particle theory of genes. The location effect is just in their favor. Goldschmidt（1938； 1955) became their most eloquent spokesman. He proposed a "modern Gene theory ”(1955: 186) to replace the particle theory. According to his new theory, there is no located gene, but only "a certain molecular pattern on a certain segment of chromosome, and any change in this pattern (the most generalized position effect) will change the role of chromosome components and thus behave as a mutant." Chromosomes as a whole are a molecular "field", Traditionally, so-called genes are discrete or even overlapping regions of the field; Mutation is the recombination of chromosome fields. This field theory and inheritance A large number of facts about science are contradictory and have not been recognized, but the fact that a well-known geneticist with rich experience, such as Goldschmidt, should put forward this theory so seriously shows that Gene theory How not consolidated. This is also reflected in many theoretical articles published from the 1930s to the 1950s (Demerec, 19381955; Muller，1945；Stadler，1954）。

Multiple allele

If there are multiple alleles in a gene, this phenomenon is called multiple allele. Any one diploid The individual only has two different alleles in the multiple alleles.

stay Complete dominance Medium, in dominant gene Homozygote and Heterozygote The phenotype of is the same. The phenotype of heterozygotes in incomplete dominance is the middle state between dominant and recessive homozygotes. This is because one gene in the heterozygote has no function, while the other gene exists Dose effect Caused by. The phenotype of heterozygote in complete dominance is that of homozygote with both overt and covert. This is due to the expression of one allele in the heterozygote.

Such as determining human ABO blood group system Each person can only have any two of the three alleles of genes IA, IB and i of the four blood groups.

Interaction

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Everything about biology phenotype Mainly protein activity Performance. In other words, almost all the traits of biology are Gene interaction Results. The so-called interaction is generally Metabolites Only a few cases involve the direct products of genes, that is, the interactions between proteins.

Nonallelic gene

basis Nonallelic gene The nature of interaction can be summarized as:

Non allelic free combination

Complementary gene

Several nonallelic genes only exist at the same time, and any mutation of these genes will lead to the same mutant character. These genes are called complementary genes.

Heterotopic dominant gene

When two non allelic genes affecting the same trait are together, the gene that can express the trait is called heterotopia Dominant gene Or called Epistatic gene 。

Additive gene

For the phenotype of the same trait, each of several non allelic genes has only a partial effect. Such several genes are called additive genes or Polygene 。 In the cumulative genes, each gene has only a small part of phenotypic effect, so it is also called micro effect gene. Relative to the minor gene, the gene that determines a certain trait by a single gene is called Major gene 。

Modifier gene

A gene that has or does not have any phenotypic effect, but exists with another mutant gene at the same time and will affect the performance of another gene. If it has the same phenotypic effect, it is not different from the cumulative gene.

Suppressor gene

When one gene mutates, the phenotypic effect of the other mutant gene disappears and the wild type phenotype is restored, which is called the former gene because of the Suppressor gene 。 If the former gene itself has a phenotypic effect, there is no difference between the suppressor gene and the heterotopic dominant gene.

Regulatory gene

If a gene has a repressing or activating effect on another gene or several genes, it is called a gene regulating gene. Regulatory genes play a role by controlling the transcription of regulated structural genes. The regulatory gene with repressive effect is different from the suppressor gene, because the suppressor gene acts on the mutant gene and is itself a mutant gene, while the regulatory gene acts on the wild type gene and is itself a wild type gene.

Minor polygene

There are many genes that affect the same character, so that their types cannot be clearly distinguished in the hybrid offspring. These genes are collectively called minor polygenes or polygenes.

Background genotype

Theoretically, the function of any gene is affected by other genes in the same cell. Except for a few genes being studied, all other genes constitute the so-called background genotype or residual genotype.

Allele

Basic type

1932 H. J. Mahler According to the relationship between mutant gene and wild type allele, it can be summarized as invalid gene, sub effect gene, super effect gene, new effect gene and counter effect gene.

Invalid gene

A mutant gene that cannot produce a wild-type phenotype and is completely inactive. General invalid genes can pass through Reverse mutation It becomes a wild type gene.

Subgene

The phenotypic effect is the same as that of the wild type in nature, but is inferior to that of the mutant gene of the wild type in degree.

Supergene

Mutants whose phenotypic effects exceed those of wild-type alleles.

Novel gene

A mutant gene that produces a new trait not found in the wild type allele.

Counter gene

A mutant gene that acts as a relative resistance to the wild-type allele.

Mosaic dominance

For a certain character, a Allele The phenomenon that affects one part of the body and another allele affects the other part of the body is called mosaic dominance.

Gene and environment

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The expression of gene function is inseparable from the influence of internal and external environment. In a group of individuals with a specific gene, the percentage of individuals showing the gene trait is called Penetrance ； In individuals with a specific gene but showing this trait, the degree of performance of this trait is called Performance 。 Both penetrance and expressiveness are affected by internal and external environment.

The internal environment refers to the gender, age and other conditions of the organism and Background genotype 。

Gender

The effect of gender on gene function is actually sex hormone Influence on gene action. Sex hormones are controlled by genes, so these are actually Gene interaction Results.

Age

Each gene in human has a very different age in showing its phenotype.

Background genotype

Through selection, the penetrance and expressiveness of a certain genetic trait of animal and plant strains can be changed, which indicates that the role of some genes is often affected by a series of modified genes or background genotypes.

The influence caused by the difference of background genotype can be minimized in the following three cases: Inbreeding Obtainable Pure line ； Monozygotic twins Children; Asexual line (including asexual reproduction lines of some higher plants, microorganisms and higher animals cell line ）。 Using these systems as experimental systems can more clearly show the impact of environmental factors and more accurately explain the role of a gene. twin method The application in human genetics and the application of homoline organisms in genetics and many biological studies are based on this principle.

External environment

temperature

Temperature sensitive mutant It can only show mutant traits in certain temperatures. For general mutants, temperature also has varying degrees of influence on the role of genes.

Nutrition

The yellow of rabbit fat is determined by homozygous state of gene y and xanthophyll The exists of. If the food does not contain lutein, then the fat of yy homozygote is not yellow. The function of y gene is obviously related to the assimilation of lutein.

evolution

In terms of the content of DNA in cells, the lower the biological content, the higher the biological content. In terms of the number and type of genes, the lower the number of organisms, the more advanced the number of organisms. The increase of DNA content and gene number is closely related to the gradual completion of physiological functions.

Gene was originally an abstract symbol, but later it was proved that it occupied a certain position on the chromosome inheritance The functional unit of. The isolation of genes in the lactose operon of Escherichia coli and the realization of transcription in vitro further demonstrate that genes are entities. Now it is possible to modify genes in test tubes (see recombinant DNA technology) or even Synthetic gene 。 Structure, function, recombination, mutation and gene expression The research on regulation and interaction of genetics The central topic of the study.

gene expression

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The process of gene expression is to transfer the genetic information on DNA to mRNA, and then translate it to protein. During translation, tRNA is responsible for binding to specific amino acids and transporting them to ribosomes amino acid Where they connect to form proteins. This process is mediated by tRNA synthetase. Once a problem occurs, the wrong protein will be generated, which will lead to disastrous consequences. Fortunately, tRNA The matching between molecules and amino acids is very accurate, but so far people still lack sufficient understanding of this mechanism.^[3]

Gene variation

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Gene variation It refers to the sudden and heritable variation of genomic DNA molecules. At the molecular level, gene variation refers to the change in the composition or sequence of base pairs in the structure of genes. Although the gene is very stable, it can cell division The stability is relative. Under certain conditions, a gene can suddenly change from its original form of existence to another new form of existence, that is, a new gene suddenly appears at a site^[4] , instead of the original gene, this gene is called the mutant gene. Thus, new traits never existed in ancestors suddenly appeared in the performance of offspring. for example The Queen of England The Victoria family had never seen it before hemophilia But one of her sons suffered from hemophilia and became the first member of her family to suffer from hemophilia. Later, several hemophiliacs appeared among her grandchildren. Apparently, there was a mutation of hemophilia gene in her father or mother. The mutant gene was passed to her, and she was heterozygous, so the phenotype was still normal, but it was passed to her son through her. The consequences of gene variation are caused by the formation of pathogenic genes as described above Hereditary disease In addition, it can also cause stillbirth spontaneous abortion And premature death after birth, which are called fatal mutations; Of course, it may also have no impact on the human body, only causing genetic differences between normal people; It may even bring certain benefits to the survival of individuals.

Smiley faced spider is caused by genetic variation

gene silencing

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According to the basic principle of heredity, if some genes can help parents survive and reproduce, parents will pass these genes on to their offspring. But some studies show that the real situation is much more complicated: genes can be turned off or silenced to cope with environmental or other factors, and these changes can sometimes be passed from one generation to the next^[5] 。

U.S.A University of Maryland Geneticists have proposed a special mechanism through which parents can Silencing gene Inherited to offspring, and this silence can be maintained for more than 25 generations^[5] 。 This discovery may change people's understanding of animal evolution and help to design a wide range of genetic disease therapies in the future. Relevant papers were published online in Proceedings of the National Academy of Sciences on February 2, 2015^[5] 。

They are interested in caenorhabditis elegans The nematode nerve cell Double stranded RNA molecules (dsRNA) matched with special genes were produced. DsRNA molecules can move between somatic cells. When their sequences match the corresponding cellular DNA, they can make gene silencing 。 This time, they found that dsRNA could also enter into germ cells, silencing genes in them. What's more surprising is that this silence can last more than 25 generations^[5] 。

Long term and stable silencing effect is crucial in the development of genetic disease therapy. Researchers have been calling“ RNA interference ”As a potential gene therapy, it can target any disease gene with paired dsRNA. The biggest obstacle is how to achieve stable silence, so that patients do not have to repeatedly use high doses dsRNA^[5] 。

gene diagnosis

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When harmful substances in the environment enter the fertilized egg or the mother, when parents have a certain common blood relationship or a certain number of genetic relationships, in these cases, genes in the genome of offspring will be defective, resulting in disease. By using gene chip and other technologies to analyze the human genome, we can find out the pathogenic Genetic defect gene Area. cancer 、 diabetes Most diseases are caused by genetic defects. Medical and biological researchers will be able to identify mutant genes that will eventually lead to cancer, etc. within seconds. With a small drop of test solution, doctors can predict the efficacy of drugs on patients, diagnose the adverse reactions of drugs in the treatment process, and identify what bacteria, viruses or other microorganisms have infected patients on the spot. Using gene chip to analyze genetic genes will enable the diagnosis rate of diabetes to reach more than 50% in 10 years.

In the future, the diagnostic robot equipped with gene chip will take blood from the examinee during physical examination, and the results of physical examination will be displayed on the computer screen in a twinkling. utilize gene diagnosis Medical treatment will go from the era of "mass medical treatment" to the era of "customized medical treatment" based on individual genetic genes, and amniotic fluid can also be drawn for prenatal genetic diagnosis.

Gene recombination

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Gene recombination It is the process of exchanging and reassembling DNA fragments and forming new DNA molecules due to the break and connection of different DNA strands. In 1974, Waclaw Szybalski, Poland, called gene recombination Synthetic Biology In 1978, he wrote in the journal Gene that restriction enzymes will lead us into a new era of synthetic biology.

Gene Samples

gene therapy

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gene therapy It is through gene cloning, transgene and other technologies to copy and produce organs matching itself, which can solve the problems of some patients with intellectual and physiological defects. Through disease analysis, gene analysis technology, synthetic gene technology, etc., we can produce matched healthy organs.

Gene mutation

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Gene mutation (gene mutation) A structural change within a gene that can be inherited, also known as point mutation , usually can cause certain phenotypic changes. Broadly defined mutations include chromosome aberration The narrow sense of mutation refers to point mutation. In fact, the boundary between distortion and point mutation is not clear, especially for micro distortion. The wild-type gene becomes Mutant Genes. The term mutant refers to both the mutant gene and the individual with the mutant gene.

gene regulation

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Mechanisms that control gene expression in organisms. The main process of gene expression is gene transcription and Messenger ribonucleic acid (mRNA). Gene regulation mainly occurs at three levels, namely: ① the level of DNA modification, the regulation of RNA transcription, and the control of mRNA translation process; ② Microbes can change their metabolic mode to adapt to environmental changes through gene regulation, which is generally transient and reversible; ③ multicellular organism The gene regulation of cell differentiation 、 Morphogenesis And the basis of ontogeny, such regulation is generally long-term, and often irreversible. The study of gene regulation has a wide range of biological significance, including genetic and molecular genetics Important research fields.

Gene computing

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DNA molecule is similar to "computer disk" and has the functions of information storage, replication, rewriting, etc. take Human cells The DNA molecules in the 23 pairs of chromosomes in the nucleus are connected and straightened, with a length of about 0.7 meters, but if it is folded, it can be reduced to a small ball with a diameter of only a few microns. Therefore, DNA molecule is regarded as a molecular memory with ultra-high density and large capacity.

After being improved, gene chips can also be used for manufacturing after expressing different numbers with different biological states Biological computer 。 Based on gene chip and gene algorithm, the future Bioinformatics It is expected that there will be hardware giants like Intel and software giants in the computer industry—— Microsoft A comparable bio information enterprise.

Gene recognition

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Due to the uniqueness of human genes (except for identical twins) forensic medicine The most widely used aspects of the above are individual identification and paternity testing.

In forensic medicine, STR loci and Mononucleotide (SNP) site detection is the core of the second and third generation of DNA analysis technology, which is followed by RFLPs（ Restrictive fragment length polymorphism ）VNTRs (variable quantity Tandem repeat sequence Polymorphism). As the most advanced criminal biotechnology, DNA analysis technology is Forensic material evidence The test provides a scientific, reliable and fast means to make the identification of physical evidence transition from individual exclusion to the level that can be identified at the same time. DNA test can directly identify crimes and provide accurate and reliable basis for the detection of major difficult cases such as murder cases, rape homicide cases, dismemberment cases, rape induced pregnancy cases, etc. With the development and application of DNA technology, the detection of DNA marker system will become an important means and approach to solve cases. This method is used as Paternity test It is already very mature and internationally recognized as the best method.

gene sequencing

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In August 2022, the Chinese Academy of Metrology and Fudan University successfully developed the whole genome DNA sequence and the whole transcriptome RNA reference material of the Chinese Family No. 1 (identical twin family) human B lymphocyte line, which was officially released at the exchange meeting on genome testing quality and measurement standards. This series of reference materials fills the gap at home and abroad, and will guarantee the reliability of gene sequencing.^[9]

Gene testing

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Gene detection is a technology to detect DNA through blood, other body fluids, or cells. Gene testing can be used to diagnose diseases and predict disease risks. Disease diagnosis is caused by gene detection technology Hereditary disease The mutant gene of. At present, the most widely used gene testing is the detection of neonatal genetic diseases, the diagnosis of genetic diseases and the auxiliary diagnosis of some common diseases. At present, more than 1000 genetic diseases can be diagnosed through gene detection technology.

Male/female tumor gene detection can predict whether they are high-risk groups and improve their health immunity through good preventive measures. Screening diseases include colon adenoma Nasopharyngeal carcinoma 、 esophageal cancer 、 leukemia 、 liver cancer 、 gastric cancer wait.

application area

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Production field

People can use Gene technology , Production transgenic food 。 For example, scientists can implant a gene that controls the growth of meat in a certain type of pig into a chicken, so that the chicken can also gain the ability to rapidly gain weight. However, some people are afraid of eating genetically modified food because of its high-tech content foreign gene Later, it will change people's genetic traits, such as eating genetically modified pork will become active, drinking genetically modified milk is prone to galactophilia, and so on. In fact, these concerns are unnecessary. All the food people eat comes from other organisms. Almost all the food contains countless DNA with heterologous genes. These DNA molecules will be degraded into single deoxyribonucleotides in the digestive tract, which can be absorbed by the human body for the construction of its own genetic material. Huazhong Agricultural University Zhang Qifa Academicians believe that:“ transgenic technology It provides new means for crop improvement, but also brings potential risks. Gene technology itself can conduct accurate analysis and assessment, thus effectively avoiding risks. The risk assessment of transgenic technology should refer to traditional technology. Scientific and standardized management can provide security for the use of transgenic technology. life sciences Science popularization and public education of basic knowledge are very important. "

Military field

biological weapon It has been used for a long time. Bacteria and toxic gas make people turn pale. But the legendary Genetic weapon But it's even more chilling.

environmental protection

We can develop special gene drugs , which can not only kill them efficiently, but also will not affect other creatures and save costs. For example, if there is a gene product that can effectively kill the water hyacinth that has been harming the freshwater area of China, it will save billions every year.

Science is a double-edged sword, and genetic engineering is no exception. We should give full play to the part of genetic engineering that can benefit mankind and curb its harm.

Medical aspects

With the deepening of human genetic research, many diseases are found to be caused by Gene structure And function change. Scientists will not only be able to find defective genes, but also master how to diagnose, repair, treat and prevent genes, which is the frontier of biotechnology development. This achievement will bring immeasurable benefits to human health and life. so-called gene therapy It refers to the use of genetic engineering techniques to transfer normal genes into the cells of diseased patients to replace diseased genes, so as to express the products that are missing, or to achieve the purpose of treating some genetic diseases by closing or reducing the abnormal expression of genes. More than 6500 genetic diseases have been found, including about 3000 caused by single gene defects. Therefore, genetic diseases are the main target of gene therapy. The first gene therapy was carried out in the United States in 1990. At that time, two 4-year-old and 9-year-old girls Adenosine deaminase He suffered from severe combined immunodeficiency due to his deficiency. Scientists have successfully treated them with gene therapy. This pioneering work marks the transition of gene therapy from experimental research to clinical trials. In 1991, the first case in China Type B blood The clinical experiment of gene therapy for comorbidity has also been successful.

The latest progress in gene therapy is the upcoming Gene gun Technology in gene therapy. The method is to introduce specific DNA into the muscle, liver, spleen, intestine and skin of mice with improved gene gun technology to obtain successful expression. This success indicates that people may use gene gun to deliver drugs to specific parts of the human body in the future to replace traditional vaccination, and use gene gun technology to treat genetic diseases.

Scientists are studying fetal gene therapy. If the experimental efficacy is further confirmed, it is possible to extend fetal gene therapy to other genetic diseases, so as to prevent newborns suffering from genetic diseases from being born, thus fundamentally improving the health level of offspring.

On June 27, 2022, at the closing ceremony of the 24th annual meeting of the China Association for Science and Technology, the China Association for Science and Technology solemnly released 10 industrial technology issues that have a leading role in industrial development, including "How to establish a clinical transformation treatment system for cells and gene therapy?" 。^[8]

Genetically engineered drugs

Genetically engineered drugs , Yes Recombinant DNA Expression product of. In a broad sense, anything that involves genetic engineering in the process of drug production can become a genetically engineered drug. The research in this field has very attractive prospects.

The development focus of genetic engineering drug research is from Protein drugs , such as insulin , people growth hormone , promote red blood cell Molecule proteins such as anabolins are transferred to search for smaller molecules Protein drugs 。 This is because the molecules of proteins are generally large and difficult to pass through the cell membrane, thus affecting their pharmacological effects Small molecule Drugs have obvious advantages in this respect. On the other hand, the treatment of diseases has also broadened, from simple medication to Genetic engineering technology Or the gene itself as a treatment.

Another problem that needs to be noticed is that many people who were conquered in the past Infectious Diseases , because bacteria produce Drug resistance , making a comeback. One of the most noteworthy is tuberculosis. according to world health organization Reported that there has been a global tuberculosis crisis. Tuberculosis, which was about to be eradicated, has resurged, and a variety of drug-resistant tuberculosis 。 According to statistics, 1.722 billion people around the world are infected with TB germs, 9 million new TB patients every year, and about 3 million people die of TB, which is equivalent to one person dying of TB every 10 seconds. Scientists also pointed out that in the future, hundreds of people infected with bacterial diseases will have no medicine to cure Viral disease More and more, it is impossible to prevent. At the same time, however, scientists have also explored ways to deal with it. They have found some small molecules of antimicrobials in human bodies, insects and plant seeds polypeptide , their molecular weight It is less than 4000, with only more than 30 amino acids. It has a strong universal killing activity against pathogenic microorganisms, and can have a strong killing effect on bacteria, bacteria, fungi and other pathogenic microorganisms. It is likely to become a new generation of“ Superantibiotic ”。 In addition to using it to develop new antibiotics, these small molecular peptides can also be used in agriculture to cultivate new varieties of disease resistant crops.

Crop cultivation

Scientists are using Genetic engineering technology Significant progress has been made in improving crops green revolution Close at hand. A prominent feature of this new green revolution is the integration of biotechnology, agriculture, food and medicine industries.

In the 1950s and 1960s, due to hybrid variety Promotion chemical fertilizer Increase in use and irrigation area, crops The output has doubled, which is known as the "green revolution". However, some researchers believe that these methods have been difficult to further improve crop yields significantly.

Gene technology The breakthrough has enabled scientists to improve crops in ways unimaginable to traditional breeding experts. For example, genetic technology can enable crops to release pesticides by themselves, enable crops to be planted on dry or saline land, or produce more nutritious food. Scientists are also developing crops that can produce vaccines and food that can prevent diseases. Gene technology has also greatly shortened the time for developing new crop varieties. Using traditional breeding methods, it takes seven or eight years to cultivate a new plant variety. Genetic engineering technology enables researchers to inject any gene into a plant, so as to cultivate a new crop variety, which will shorten the time by half.

Although the first varieties of genetically engineered crops have only begun to appear on the market, half of the corn, soybeans and cotton planted in the United States will use seeds cultivated by genetic engineering. It is estimated that the market size of genetically engineered agricultural products and food in the United States will expand from US $4 billion to US $20 billion in the next five years and reach US $75 billion 20 years later. Some experts predict that "by the beginning of the 21st century, every kind of food in the United States will probably contain a little genetic engineering."

Although many people, especially consumers in European countries GM agricultural products However, experts pointed out that it is imperative to use genetic engineering to improve crops. This is due to the increasing pressure of the global population. Experts estimate that the global population will increase by half in the next 40 years, and for this reason, food production needs to increase by 75%. In addition, the aging of the population Medical system It is necessary to develop foods that can enhance human health.

Accelerating the cultivation of new crop varieties is also a common goal of developing biotechnology in the developing countries of the third world Agricultural biotechnology Its research and application have been widely carried out, and remarkable benefits have been achieved.

Molecular Evolution Research

Molecular processing Cheng is the third generation of genetic engineering after protein engineering. It is based on the Multimolecular system Apply selective pressure to simulate nature Biological evolution To create new genes and proteins.

This requires three steps, namely amplification, mutation and selection. Amplification is to obtain a large number of copies of DNA fragments of extracted genetic information; Mutation is to exert pressure at the gene level to make the bases on DNA fragments mutate, which provides raw materials for selection and evolution; Selection is to fix variation at the phenotypic level by survival of the fittest and elimination of the fittest. These three processes are closely linked.

Scientists have used this method to Directed evolution , can inhibit thrombin Active DNA molecules, which have anticoagulant effect, may replace protein drugs that dissolve thrombus to treat myocardial infarction 、 cerebral thrombosis And other diseases.

Gene function

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Biological function, such as as protein kinase Carry out Phosphorylation modification; cytology Functions, such as participating in intercellular and intracellular signal transmission Pathway; Developmental functions, such as participation in morphogenesis.

Gene origin

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Gene is compilation amino acid Of Codon Therefore, the origin of codon is the origin of gene. Except for a few differences, the genetic codes of known organisms on the earth are very close; Therefore, according to Evolutionism The genetic code should appear very early in the life history. The existing evidence shows that the setting of genetic code is not a random result, which may be explained as follows:^[6]

ATP is located at the center of biochemical system in cells

Carl Richard Woese believes that some amino acid Corresponding to them Codon Selective chemical binding (stereochemical hypothesis, stereochemical hypothesis）， This shows that the complex protein manufacturing process may not have existed for a long time, and the original protein may have been formed directly on nucleic acid. However, J. Tze Fei Wong believes that the fidelity of amino acids and corresponding codes reflects the similarity of amino acid biosynthesis paths, not the similarity of physical and chemical properties (coevolutionary hypothesis, co-evolution hypothesis）。 Xie Ping proposed that, Genetic code As a part of the biochemical system, it must be related to the evolution of the biochemical system. The core of the biochemical system is ATP, and only it can be established nucleic acid and protein Links between（ ATP center hypothesis ， ATP-centric hypothesis）。

The original genetic code may be much simpler than it is today. With the evolution of life, new amino acids are produced and reused, making the genetic code more complex. Although many evidences prove this view, the detailed evolution process is still under exploration. after natural selection , current Genetic code Reduced mutation Adverse effects caused. Knight et al. believe that genetic code is affected by three factors, selection, history and chemistry, at different stages (comprehensive evolutionary hypothesis).

Schematic Diagram of ATP Center Hypothesis

Other hypotheses: Aigen In vitro selection hypothesis was proposed, Leslie Eleazer Orgel proposed the origin hypothesis of decoding mechanism, and Christian de Duve proposed the second genetic code hypothesis. Wu et al speculated that the triplet code evolved from two types of triplet codes according to Triad password It is divided by the fixed base position in, including prefix codons and suffix codons. However, Baranov et al speculated that Triplet codon It evolved from longer codons (such as quadruplet codons), because long codons Codon More coding redundancy to resist larger mutation Pressure.

scientific research

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The time of female fertility is related to genes. Through research, scientists have found that specific genetic variations can make the fertility period longer and the menopause later, so that some women have a fertility rate of 10% higher than that of ordinary people. Professor Mills and 250 other researchers, through statistics and analysis of 330000 male and female fertility information, found that genes can affect a person for the first time a sexual behavior The time of first pregnancy and the time of menopause^[7] 。

In 2023, in terms of gene sequencing, the UK announced that it would sequence the genomes of 100000 newborns; The British Biological Bank has released the world's largest whole genome sequencing database, which is expected to bring about changes in global diagnosis, treatment and cure; Cambridge University scientists have proposed a new DNA sequencing method, which can detect the interaction between small molecule drugs and specific locations of the genome, and is expected to provide a lot of new insights on how some drug therapies interact with the human genome. In the field of cancer treatment, Cambridge University scientists have identified at least four new genes related to breast cancer. In addition, Germany Max Planck The researchers of the Institute of Molecular Cell Biology and Genetics have developed a new method for gene comparison of hundreds of animals, which can accurately identify orthologous genes.^[10]

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