What is Genetic Mutation?

A sudden, heritable mutation in a genomic DNA molecule. At the molecular level, genetic mutation refers to a change in the structure or arrangement of base pairs in a gene. Although genes are very stable and can replicate themselves precisely when cells divide, this stability is relative. Under certain conditions, a gene can also suddenly change from its original form of existence to another new form of existence, that is, at a site, a new gene suddenly appears instead of the original gene. This gene is called a mutant gene. So the performance of future generations suddenly appeared new traits that ancestors never had.

A sudden, heritable mutation in a genomic DNA molecule. At the molecular level, genetic mutation refers to a change in the structure or arrangement of base pairs in a gene. Although genes are very stable and can replicate themselves precisely when cells divide, this stability is relative. Under certain conditions, a gene can also suddenly change from its original form of existence to another new form of existence, that is, at a site, a new gene suddenly appears instead of the original gene. This gene is called a mutant gene. So the performance of future generations suddenly appeared new traits that ancestors never had.

Structural changes that can be inherited within one gene. Also known as point mutations, they can cause certain phenotypic changes. Broadly defined mutations include chromosomal aberrations. Narrow mutations are specifically point mutations. In fact, the boundaries between distortions and point mutations are not clear, especially for small distortions. Wild-type genes are mutated into mutant genes. The term mutant refers to both the mutant gene and the individual with the mutant gene.

Gene mutations can occur at any stage of development, usually during the period of DNA replication, that is, the cell division period, including the mitotic and meiotic periods; at the same time, the gene mutation and DNA replication, DNA damage repair, canceration and Ageing is related, and gene mutation is also one of the important factors in biological evolution. Therefore, studying gene mutation has broad biological significance in addition to its theoretical significance. Gene mutations provide mutants for genetic research and materials for breeding work, so it has practical significance in scientific research and production.

Chinese name

Gene mutation

Foreign name

genic mutation

Presenter

E. Fritz

Presentation time

1959

Applied discipline

biological

Scope of application

medicine

Gene mutation development

Gene mutations were first discovered in Drosophila by TH Morgan in 1910. HJ Mahler first induced mutations in Drosophila and Maize in 1927 and LJ Stadler in 1928, respectively. In 1947, C. Auerbach used a chemical mutagen for the first time, inducing mutations in fruit flies with nitrogen mustard. In 1943 SE Luria and M. Delbrück first demonstrated in E. coli that the emergence of resistance to phage was the result of genetic mutations. The same conclusion was then reached on the resistance of bacteria to streptomycin and sulfa drugs. Therefore, the general phenomenon of biological mutation in the biological world is gradually fully understood, and the study of genetic mutation has entered a new period. After the discovery of photoresurrection in 1949, research on DNA damage repair has also advanced rapidly. The results of these studies indicate that gene mutation is not a simple chemical change, but a complex process related to the action of a series of enzymes.

In 1958, S. Benzer discovered that the r gene of bacteriophage T4 has a particularly susceptible mutation site, a hot spot, and pointed out that the change of a pair of nucleotides of a gene is related to its position.

In 1959, E. Fritz proposed the theory of base substitution for gene mutation, and in 1961, FHC Crick et al. Proposed the frame-shift mutation theory (see genetic code). With the development of molecular genetics and the emergence of technologies such as DNA nucleotide sequence analysis, the types of DNA molecular structural changes brought about by genetic mutations, including some hot molecular structures, have been able to be targeted for mutagenesis. .

Gene mutation

Gene mutations can be spontaneous or induced. There is no essential difference between spontaneous gene mutations and induced gene mutations, and the role of gene mutation mutagens only increases the mutation rate of genes.

Schematic of base substitution

According to phenotypic effects, mutants can be divided into morphological mutants, biochemical mutants and lethal mutants. This distinction does not involve the nature of the mutation and is not strict. Because morphological and lethal mutations must have their biochemical basis, strictly speaking, all mutations are biochemical mutations. According to the situation of base changes, gene mutations can be generally divided into two major types: base substitution mutations and frameshift mutations.

(subsititution) Gene mutation base substitution mutation (subsititution)

Refers to a mutation caused by the replacement of one base pair by another base pair in a DNA molecule, also known as a point mutation . Point mutation is divided into two forms of conversion and transversion. If a purine is replaced by another purine or a pyrimidine is replaced by another pyrimidine, it is called a transition (transitio

BU-induced mutation

n). Mutations of purine-substituted pyrimidines or pyrimidine-substituted purines are called transversions. Since there are four bases in the DNA molecule, four transitions and eight transversions may occur (see above). In naturally occurring mutations, there are more transitions than transversions.

The conversion of base pairs can be caused by the incorporation of base analogs. For example, 5-bromouracil (BU) is a compound similar to thymine. It has two structures, keto and enol, and the two can be changed. Generally, keto is easier to change to ene. Alcoholic. When DNA is copied, keto BU replaces T, making AT base pair A-BU; in the second copy, enol BU can pair with G, so G-BU base pair appears; third time When copying, G and C are paired, resulting in GC base pairs. In this way, the original AT base pairs become GC base pairs (see left picture).

Nitrosamine-induced mutation

Base pair switching can also be caused by mutagenesis of some chemical mutagens. For example, nitrite can oxidatively deaminate cytosine (C) into uracil (U). In the next replication, U is not paired with G, but is paired with A; the result of replication is CG and becomes TA (see the right picture) . For another example, mustard gas and diethyl sulfate in an alkylating agent can ethylate G and become alkylated guanine (mG). As a result, mG is not paired with C, but is paired with T. After replication, GC changes For AT.

translocation Gene mutation frameshift (translocation)

Refers to a mutation that causes a series of coding sequences after the insertion or loss of a sequence to be misplaced when one or more (not a multiple of 3 or 3) base pairs are inserted or lost at a certain position in a DNA fragment. It can cause abnormal genetic information after this locus. Genes with frameshift mutations can cause changes in the amino acid sequences that make up the polypeptide chain when they are expressed, thereby seriously affecting the structure and function of the protein or enzyme. Acridine-type mutagens such as proxanthin, acridine, acridine orange, and the like are relatively flat and can be inserted between adjacent base pairs of a DNA molecule. If inserted before DNA replication, it will result in the insertion of 1 base pair; if inserted during the replication process, it will cause the deletion of 1 base pair. Both results will cause frame-shift mutation.

(deletion) Gene mutation deletion

Genes can also be mutated due to the deletion of longer stretches of DNA. If the deleted range includes two genes, it seems that the two genes are mutated at the same time, so it is also called multi-site mutation. Mutations caused by deletions do not occur back mutations. So strictly speaking, the deletion should be a chromosomal aberration.

(insertion) Gene mutation insertion mutation

If a piece of foreign DNA is inserted into the DNA of a gene, its structure is destroyed and a mutation is caused. E. coli bacteriophage Mu-1 and some insertion sequences (IS) and transposons (see transposable elements) are genetic factors capable of transferring positions. When they are transferred into a gene, this gene is mutated . Many transposons carry a drug resistance gene. When they are transferred to a certain gene, they cause mutations on the one hand and a drug resistance gene on this position on the other. The inserted DNA molecule can be lost by cleavage, and accurate cleavage can restore the mutant gene to a wild-type gene. The frequency of this event did not increase with mutagen treatment.

Gene mutation characteristics

Whether it is a mutation of eukaryotes or prokaryotes, or whatever type of mutation, it has the common characteristics of randomness, low frequency and reversibility.

Gene mutation universality

Gene mutations are common in all species in nature.

Genetic mutation randomness

TH Morgan accidentally found a white compound eyed fruit fly among many red compound eyed fruit flies. This fact indicates that the genetic mutation occurs randomly in time, in the individual who has the mutation, and in the gene in which the mutation occurs. The numerous mutations found in higher plants in the future all explain the randomness of gene mutations. The situation is far more complicated in bacteria. When bacteria are cultured in a medium containing a certain drug, bacteria that are resistant to the drug can often be obtained. Therefore, it was thought that the drug resistance was caused by drugs and was directed adaptation rather than random mutation. S. Luria and M. Delbrück first demonstrated in 1943 that the presence of phage-resistant bacteria in E. coli was unrelated to the presence of bacteriophage using a wave test method. J. Lederberg et al. Also confirmed this argument with the imprinting method in 1952. The method is to coat a large number of drug-sensitive bacteria on the surface of the drug-free culture medium, and use a piece of sterilized velvet as an inoculation tool to inoculate the surface of the culture medium containing a drug, so that two The positions of the colonies on the petri dishes are all one to one. According to the position of individual colonies growing on the surface of the latter medium, corresponding colonies can be found on the previous culture dish. In many cases these colonies can be seen as resistant. Because the former medium is drug-free, the results of this experiment very intuitively show that the emergence of drug resistance does not depend on the presence of the drug, but is the result of random mutations, which is only detected by the drug.

Rare mutations

When the first mutant gene was found, instead of several white compound eyes, only one was found, indicating that the mutation is extremely rare, that is, the wild-type gene mutated at a very low mutation rate (some representative Gene mutation rates are shown in the table). In sexually reproduced organisms, the mutation rate is expressed by the probability of mutation of each gamete, that is, the number of mutant gametes in a certain number of gametes. Among asexually reproduced bacteria, the mutation rate is expressed by the probability of mutation of each bacterium in each cell generation, that is, the number of mutations of a certain number of bacteria during one division. It is estimated that among higher organisms, only about 10 ^ 5 ~ 10 ^ 8 germ cells have a gene mutation. Although the frequency of genetic mutations is low, when there are many individuals in a population, it is possible to generate a variety of random mutations, which is sufficient to provide rich heritable mutations.

Gene mutation reversibility

The process of mutating a wild-type gene into a mutant gene is called forward mutation. The rarity of forward mutations indicates that the wild-type gene is a relatively stable structure. Mutated genes can be mutated to become wild-type genes, a process called back mutation. It can also be seen from the table that back mutations are rare, indicating that the mutant gene is also a relatively stable structure. However, the forward mutation rate is always higher than the reverse mutation rate. This is because structural changes in many positions within a wild-type gene can cause a gene mutation. Restore.

Mutations are less beneficial

Gene mutations generally have adverse effects, are eliminated or die, but there are very few species that make the species more adaptable.

Non-specific mutation

For example, the black hair A gene may be mutated into the a + gene that controls white hair or the a- gene that controls green hair.

Gene mutation benefit

Gene mutations are generally harmful, but very few are beneficial mutations. For example, a bird's mouth is very short. After a sudden mutation, the mouth will become longer, which will easily catch food or water.

Explains the obvious differences in a bird's genetic mutation or evolution

Generally, the body sends out antibodies or other restorations to repair itself after a mutation. But some mutations are irreversible. Mutations can lead to immediate death, but can also have dire consequences, such as the failure of organs to function properly, severely damaged DNA, and poor body immunity. If it is a beneficial mutation, miracles may occur, such as special variant cells in the body's secretion to protect the organs, the body, or the growth of bones in some areas that are not protected by bones. Genes and DNA are like an identity card for everyone, but he is also a prophet of a person, because it determines the age of the body, disease and death.

Mutation independence

Mutation of one allele at a certain locus does not affect the other allele, that is, two genes in the allele will not be mutated at the same time.

Recessive mutation: no performance in contemporary, F2 generation.

Dominant mutation: contemporary manifestations, coexisting with the original traits, forming mosaic phenomena or chimeras.

Genetic repeatability

The same mutation can occur multiple times between different individuals in the same organism.

Gene mutation effect

Whether it is a base substitution mutation or a frameshift mutation, it can change the amino acid composition or sequence in the polypeptide chain, and then affect

Gene mutation

It affects the biological functions of proteins or enzymes, which makes the body's phenotype abnormal. The effects of base mutations on the amino acid sequence in a polypeptide chain are generally of the following types.

Gene mutation synonymous mutation

Same sense mutation: after base substitution, although each codon becomes another codon, the amino acid encoded by the codon is changed due to the degeneracy of the codon, Therefore, the mutation effect does not actually occur. For example, the third G of GCG in the template chain of DNA molecule is replaced by A and becomes GCA, then the corresponding codon CGC in mRNA becomes CGU. Since CGC and CGU are codons that encode arginine, they are mutated The gene product (protein) before and after is exactly the same. Synonymous mutations account for about 25% of the total number of base substitution mutations.

Gene mutation missense mutation

Missense mutation: A mutation in a base pair that causes a codon in an mRNA to become a codon encoding another amino acid is called a missense mutation. Missense mutations can cause structural or functional abnormalities in certain proteins or enzymes in the body, which can cause disease. For example, the sixth position of human normal hemoglobin chain is glutamic acid, whose codon is GAA or GAG. If the second base A is replaced by U, it becomes GUA or GUG, and glutamic acid is replaced by valine. Instead, the formation of abnormal hemoglobin HbS results in individuals with sickle cell anemia, which has a mutation effect.

Nonsense mutation

Nonsense mutation: a mutation in a code encoding an amino acid is a stop code, and the polypeptide chain synthesis is terminated early

Gene mutation

It produces non-biologically active polypeptide fragments, called nonsense mutations. For example, when G in ATG in a DNA molecule is replaced by T, the codon on the corresponding mRNA chain changes from UAC to UAA, thus stopping translation and shortening the peptide chain. This mutation affects the function of the protein or enzyme in most cases.

Gene mutation termination code mutation

Terminator codon mutation: A mutation in a stop codon in a gene that encodes a codon for an amino acid is called a stop codon mutation. Because peptide chain synthesis does not stop until the next stop code appears, an excessively long polypeptide chain is synthesized, so it is also called an extension mutation . For example, human hemoglobin alpha chain mutant Hb Constant Spring has 31 amino acids more than normal human alpha globin chains.

Factors Affecting Gene Mutation

Gene mutation

Physical factors: x-ray, laser, ultraviolet, gamma rays, etc.

Gene mutation

Chemical factors: nitrous acid, aflatoxin, base analogs, etc.

Biological factors: certain viruses and bacteria.

Internal cause of gene mutation

During DNA replication, the number, order, and type of deoxynucleotides inside the gene changed locally, which changed genetic information

Gene mutation application

For humans, genetic mutations can be useful or harmful.

Mutation mutation breeding

By inducing a large number of genetic mutations in organisms, excellent breeds can be bred as needed. This is a gene mutation.

Gene mutation

Become useful. Before the discovery of chemical mutagens, plant breeding work mainly used radiation as a mutagen; after the discovery of chemical mutagens, the mutagenesis means increased greatly. In the mutation breeding of microorganisms, since it is easy to deal with a large number of individuals in a short time, it is generally only required that the mutagens have a strong effect, that is, it is required to generate a large number of mutations. For higher plants that are difficult to handle a large number of individuals in a short period of time, it is required that the effect of the mutagens is strong, efficient and specific. The so-called higher efficiency is to produce more genetic mutations and fewer chromosomal aberrations. The so-called specificity is to produce a specific type of mutation. The key technology for Israel to cultivate "colored green peppers" is to send the green pepper seeds to space to cause genetic mutations to breed in total weightlessness.

Genetic mutation pest control

Treating male pests with mutagens to cause lethal or conditionally lethal mutations, and then releasing these male pests enables them to compete with wild male insects to cause lethality

Gene mutation

Or sterile offspring.

Genetic mutation detection

Most mutations are harmful to the organism itself, and the occurrence of human cancer is also closely related to genetic mutations. Therefore, the detection of mutagenic substances in the environment has become an important task of public health.

Genetic mutation detection method

From the nature of gene mutation, detection methods are divided into three types: dominant mutation method, recessive mutation method and back mutation method. Dominant lethal mutation method: male mice are treated with the test substance, the treated male mice and untreated female mice are mated, and the number of stillbirths in the uterus of the female rats is observed. The greater the number of stillbirths, the more dominant lethal mutations are induced More. This method is suitable for chronic treatment, and has the advantages of greater reliability and the test subject is a mammal. The disadvantage is that it cannot distinguish the mutagenic effects of drugs on genetic material and other toxicological effects on embryo development. Recessive mutation method. Generally, certain plants and animals with a recessive mutation gene in a heterozygous state are used as the test object. If this recessive trait appears after treatment with a certain drug, it indicates that the drug induced the recessive mutation. There are multiple lines of heterozygous recessive mutant genes in mice, which can be used to simultaneously detect genetic mutations induced in several seats. The advantage of this method is that the mutations detected in mammals are detected. The disadvantage is that the sensitivity is low, and special animal and plant strains must be provided. The experimental period is also long. The CIB method is a detection method using fruit flies as a test object. It is mainly used to detect recessive lethal mutations on the X chromosome. Drosophila has a short life cycle, so the experimental period of this method is also short. Reverse mutation method, a method for detecting mutagenic substances based on the frequency of reversion mutation induction. It was pioneered by B. Ames in 1973, also known as Ames test. Test subjects were several histidine-deficient strains of Salmonella typhimurium, including base substitution mutants and frameshift mutants. Also included in the detection system is a rat liver microsomal activation system (S9), in which enzymes can convert some of the pre-mutagens into mutagens. Although the test object here is bacteria, not mammals, but because this detection system is simple and easy to use and has high sensitivity, it is often used as a short-term test system for the preliminary screening of mutagenic substances. This method has been used for several hundred These substances have been tested and found that about 90% of carcinogens have mutagenic effects. The intermediate host diffusion box method, in order to make the reverse mutation method closer to the situation in mammals, some people put the test cells in a special small box, the membrane of the small box only allows the solution to pass. This small box is buried in the abdominal cavity of the animal, and the animal is treated with the substance to be tested. After a certain period of time, the small box is taken out, and the number of cells in which the reverse mutation is induced is measured.

In addition to the many methods used to detect genetic mutations, there are many test systems used to detect chromosomal aberrations and sister chromatid swaps. Of course, the most reliable measurement of the carcinogenic activity of a drug is the detection of carcinogenicity in mammals. However, it is still of great practical significance to use the index of inducing reverse mutations in microorganisms as a preliminary screening for carcinogens (see toxicological genetics).

Gene mutation induction mechanism

Gene mutation base substitution mutation

This can be done through two pathways, namely the involvement of base structure analogs and chemical changes caused by mutagens or radiation.

Participation of analogs 5-Bromouracil (BU) is a structural analog of thymine. It simply replaces the methyl group of thymine (-GH3) with a bromine atom at the 5th carbon atom, and is therefore more likely to appear in enol form (Figure 2). Gene mutation

After E. coli was cultured in a medium containing BU, a part of thymine in the DNA of the bacteria was replaced by BU, and finally a small number of mutant bacteria could be found in the culture. The larger the amount of BU, the more mutants became many. Mutant bacteria do not change their mutant traits when cultured for a long time in a medium that does not contain BU. However, after culturing mutant bacteria in a medium that contains BU, a small number of wild Type bacteria. The mutagenic effect of BU can be expressed. First, in the process of DNA replication, keto BU replaced thymine T and A: T base pairs were changed to A: BU. In the next DNA replication, the enol BU * and guanine G were paired to produce G: BU. Base pairs, and finally in another replication, guanine G and cytosine C were paired and finally G: C base pairs appeared, completing the base substitution. Here, the role played by BU is to facilitate this substitution. The reason for this is that the enol-type pyrimidine appears more frequently after the bromine atom at the 5-position of the pyrimidine has replaced the methyl group.

The same theory can also be used to explain how BU induces substitution mutations or mutant back mutations (Figure 4)

Other base structural analogs such as 2-aminopurine also have mutagenic effects.

Chemical changes caused by drugs or radiation Nitrite can act on the amino group of adenine (A) to make it hypoxanthine (HX); it can act on cytosine (c) to make it uracil (U) . The change of these two amino groups to keto groups brings about a change in the base-pairing relationship, thereby causing A: T G: C or G: C A: T substitution by DNA replication.

Hydroxylamine only reacts specifically with cytosine, so it almost only induces substitution G: C A: T and does not induce A: T G: C substitution. In addition, low pH or high temperature can cause DNA molecules to lose bases, especially purines, leading to base substitutions.

Ultraviolet radiation irradiates adjacent bases on DNA molecules to form dimers, mainly thymine dimer TT. The formation of dimers causes DNA double strands to assume an abnormal configuration (see DNA Damage Repair), which can cause lethal effects or cause gene mutations, including many types of base substitutions.

Gene mutation frameshift

There are fewer types of mutagens that induce frameshift mutations, mainly acridine dyes (Figure 6). These dye molecules can be embedded in DNA molecules, causing errors in DNA replication to cause frameshift mutations.

Gene mutation directed mutagenesis

Recombinant DNA technology is used to make specific changes in DNA molecules at specified positions, thereby receiving targeted mutagenesis. For example, the DNA molecule is treated with a certain restriction endonuclease, and then the nuclease S1 that breaks down the single strand of DNA is removed to remove the single-stranded part of the two sticky ends, and then the two blunt ends are phage-t4 Ligation, so that a mutant with a few nucleotides corresponding to the recognition site for this restriction enzyme was deleted. Conversely, if DNA polymerase I is added in the presence of four deoxynucleoside triphosphates (dNTPs), the complementary synthesis results in two blunt ends with a corresponding number of nucleotides. Under the treatment of T4 contiguous enzyme, a mutant with several nucleotide repeats can be obtained at the same position.

Substitutional mutations can also be induced at specific positions. The mutagen sodium bisulfite can deaminate cytosine to become uracil, but this effect is limited to cytosine on the single strand of DNA and has no effect on cytosine on the double strand. Treat the DNA molecule with a restriction enzyme containing a cytosine in the recognition site to expose the cytosine in the sticky ends (for example, the recognition site of Hind is that the sticky end is obtained after treatment with the restriction enzyme Hind. One cytosine is exposed). After treatment with sodium bisulfite, cytosine (c) becomes uracil (U). The original base pair C: G is transformed into T: A by DNA replication. Such a base substitution mutation at a specified position is induced.

It is also possible to introduce synthetic oligonucleotide fragments into the genome and change a certain gene in a certain way.

Spontaneous mutation

The so-called spontaneous mutation refers to a mutation that occurs without treatment with a mutagen. From the results of the research on the mechanism of mutagenesis, the causes of spontaneous mutation are no more than the following. Background radiation and environmental mutagenesis. Short-wave radiation is available at any time in the universe. Experiments show that there is no threshold effect on the mutagenic effect of radiation, that is, any weak dose of radiation has a certain degree of mutagenic effect, so a small part of the spontaneous mutation may be induced by short-wave radiation. Some people estimate that this part of the fruit fly mutation accounts for about 0.1% of spontaneous mutations. In addition, exposure to mutagens in the environment is one reason for spontaneous mutations. The role of mutagenic substances produced by the organism itself. Hydrogen peroxide is a mutagen. Addition of catalase when using hydrogen peroxide as a mutagenesis treatment can reduce the mutagenesis effect. If potassium cyanide (KCN) is added at the same time, the mutagenesis effect will be improved again. This is because KCN is an inhibitor of catalase. In addition, it was found that adding KCN to the cell population without mutagenesis treatment can increase the rate of spontaneous mutation, indicating that hydrogen peroxide produced by the cell itself is the cause of part of the spontaneous mutation. Some mutagenic substances have been found in some higher plants and microorganisms, and mutagenic extracts have also been obtained in long-term stored onion and tobacco seeds. Base isomerization and interconversion. The natural base structural analog, 5-bromouracil, can induce base substitution mutations because the bromine atom at position 5 (Figure 2) causes BU to appear more in the enol structure. Under normal circumstances, the isomerization and interconversion between keto and enol forms also occur at a very low frequency, and it must also cause some spontaneous mutations that do not originate from environmental factors. In addition, it is speculated that the isomerization and interconversion between amino and imino is also a cause of spontaneous mutation. Strictly speaking, this is the true spontaneous mutation. Nucleotides can also have other forms of isomerization and interconversion, and they may also be the cause of spontaneous mutation.

Factors Affecting Gene Mutation

Internal factors

A mutation is the result of a series of changes. The factors that affect any part of this series of changes will have a certain effect on the emergence of mutations.

Mutants must first enter the cell before they come into contact with DNA in order to induce mutations. The reason why higher plants are less sensitive to the mutagenic effects of UV is because UV does not easily penetrate its cell walls. The penetration of chemicals is strongly related to the structure of the cell membrane. Salmonella typhimurium has a mutant deep roughness (rfa) that changes the composition of cell membranes, which increases the permeability of cell membranes to many drugs, thereby increasing the sensitivity of cells to many chemical mutagens.

Enzymes in the cell can destroy the mutagen that enters the cell, thereby weakening the mutagenic effect. For example, catalase can attenuate the mutagenic effects of hydrogen peroxide. Some non-mutagenic substances can also be converted into mutagens due to the activation of enzymes in cells. These substances are called promutagenic agents. For example, anthraxone itself does not have mutagenic effects, but can be converted into a mutagen, the anthraxone, by the action of hydroxylase in the liver (Figure 7).

Gene mutation

After the mutagen contacts the DNA, it can cause local damage to the DNA. If these damages are not repaired, they can hinder the replication of DNA and cause cell death. There are two types of mechanisms for repairing DNA damage: one is called error-free repair, which restores DNA to its original state without mutation; the other is called error-prone repair or error-prone repair, which allows DNA replication to continue, but also Gene mutations often occur at the same time.

Changes in cell enzyme activity related to DNA damage repair can alter the cell's response to the killing or mutagenic effects of mutagens. When a gene mutation inactivates any one of the enzymes involved in DNA damage repair, it will inevitably cause the cell to become more sensitive to the killing effect of ultraviolet or other mutagens. But in terms of mutagenesis results, it depends on whether the enzyme involves error-free repair or is prone to error repair. If it belongs to the former, then the mutation of the related gene will make the mutation more likely to occur. If it belongs to the latter, then the mutation of the related gene will make the mutation less likely to occur. Therefore, these mutant types are called mutation genes and resistance genes, respectively. . In E. coli phage T4, gene 43 encodes a DNA polymerase. There are two mutant types of gene 43. One is a mutagenesis gene whose ratio of exonuclease activity and polymerase activity of DNA polymerase is smaller than that of wild-type DNA polymerase; the other is a mutagenic gene whose ratio of these two activities of DNA polymerase is greater than wild-type DNA polymerase. Mutagenic genes have also been found in other organisms such as E. coli, yeast, and some eukaryotes.

Gene mutation

1. Sickle-cell anemia ^[1]

(1) Symptoms The red blood cells change from a normal pancake shape to a sickle type, causing the red blood cells to fail to gather together through the capillaries, and the red blood cells rupture (haemolysis), causing anemia.

(2) Base substitution in the etiology gene. Direct cause: Changes in the molecular structure of hemoglobin. Root cause: Changes in the genetic structure that controls the synthesis of hemoglobin molecules.

2.Gene mutations

Concept: A change in the genetic structure caused by the replacement, addition, and deletion of base pairs in a DNA molecule.

External factors

Temperature, gene mutation includes a series of biochemical changes, so temperature has a certain effect on gene mutation. In E. coli, the histidine-deficient (his-) in the range of 15 ° C to 37 ° C increases the spontaneous back mutation rate by 1 to 1.5 times for every 10 ° C increase, and no spontaneous mutation occurs at 0 ° C. The temperature coefficient of lethal mutation in Drosophila is also in this range. In microorganisms and fruit flies, short-term temperature changes, especially treatments at higher temperatures that are not suitable for survival, can induce mutations; in fruit flies, mutations at -6 ° C have been reported to induce mutations. Culture medium component, SOS is a kind of error-prone repair mechanism that appears after induction. As with the induction of enzyme synthesis, protein synthesis is an essential factor for the SOS mechanism in bacterial cells, so all factors affecting protein synthesis in the medium will affect gene mutations. Antimutagenic agent and mutagenic agent, substances that can promote the effect of another mutagenic agent are called mutagenic agents. For example, charred tryptophan produces two mutagens and mutagenic agents.

Nitrosoguanidine (NTC) is known to be a highly effective mutagen. Under certain conditions, the mutagenic effect of NTG can be reduced by the sulfur compounds in cobalt chloride and living red blood cells, indicating that certain substances in cobalt chloride and red blood cells have antimutagenic effects. These substances that reduce the rate of spontaneous or induced mutations are called antimutants. In addition, certain peptides such as albumin have also been shown to be anti-mutagenic agents.

Genetic mutation causes cancer cells to commit suicide

WASHINGTON: Reuters, Washington-Researchers are reporting that when scientists insert a small genetic mutation into cancer cells, their growth slows to the level of "suicide" in the cell.

Gene mutation

"It's like a poison needle," said Elizabeth Blackburn, a professor of biochemistry and biophysics at the University of California, San Francisco. "You just need to add a little bit to get significant results."

The goal of this mutation is a highly active enzyme called telomerase in cancer cells that helps maintain chromosomal structure during the depletion of cell replication.

The mutation uses telomerase to destroy rapidly expanding cancer cells-Blackburn likens this strategy to judo, where both sides use their opponent's power to defeat each other.

In this study, scientists inserted a small mutation in RNA into the enzyme's genetic code. The mutated RNA blocks the reverse transcription of telomerase into RNA to restore the normal activity of chromosomal parts that are lost during cell replication.

"Cancer cells are a well-known type of cell that fights suicide signals, and that's one of the reasons why cancer cells are so scary. It's amazing to have such a small amount of telomerase to work so effectively," Blackburn said.

In the study, low levels of mutated RNA greatly reduced the growth rate of breast and prostate cancer cells, and caused more cells to die.

This mutation reduced breast cancer tumors in living mice into which the mutant enzyme was introduced.

Although the cause of the effects of telomerase mutations on cancer cell growth is unclear, Blackburn said further

Gene mutation

The study may find that human-derived cancer cells are more sensitive to mutant enzymes than laboratory-cultured cells used in the study.

The study, completed by Blackburn and colleagues, is published in the latest issue of Proceedings of the National Academy of Sciences. Scientists have been studying several ways to treat cancer by disrupting telomerase activity, but this study by the University of California provides new treatments. "The telomerase mutation has several clear theoretical advantages as a method that directly affects tumor cells to treat cancer," said Richard Hodes of the National Institutes of Health.