Mutation refers to the variation of genetic material. Broadly speaking, mutation can be divided into two categories: chromosome aberration and gene mutation. Narrow sense mutation usually refers to gene mutation, which refers to the change of gene structure caused by substitution, addition and deletion of base pairs in DNA molecules, including point mutation caused by single base change, or deletion, repetition and insertion of multiple bases. Mutations can be divided into four types: base substitution mutation, frame shift mutation, complete code mutation, chromosome mismatch and unequal exchange.
(1) base substitution mutation: the mutation caused by the substitution of one base by another base is called base substitution mutation. For example, GC base pairs in DNA molecules are replaced by CG or AT or TA, and AT base pairs are replaced by TA or GC or CG. The process of base substitution is only to change the codon of the replaced base, that is, only one codon is changed at a time, and other codons are not involved. According to the influence of base substitution in polypeptide chain on amino acid sequence, mutations can be divided into four types: synonymous mutation, missense mutation, nonsense mutation and termination code mutation.
① Synonymous mutation: Due to the degeneracy of codons, a single base substitution may only change a specific codon on mRNA, but it does not affect the amino acid it encodes. For example, if the third G of GCG in the template chain of DNA molecule is replaced by A as GCA, the corresponding codon CGC in mRNA will be transcribed into CGU. Because CGC and CGU are both codons of arginine, the newly formed polypeptide chain has no change in amino acid order and quantity. This mutation is called synonymous mutation.
(2) missense mutation: it means that the base substitution in DNA molecules not only changes the specific genetic code on mRNA, but also causes one amino acid in the newly synthesized polypeptide chain to be replaced by another. This condition is called missense mutation. Missense mutation often leads to protein anomaly.
③ Nonsense mutation: When a single base substitution leads to the appearance of termination codes (UAG, UAA, UGA), the polypeptide chain will terminate its synthesis in advance, and most of the generated protein will lose its activity or normal function. This mutation is called nonsense mutation. For example, when the G of ATG in the template chain of DNA molecule is replaced by T, the codon on the corresponding mRNA changes from UAC to UAA, so translation stops here and the peptide chain becomes shorter.
④ Termination codon mutation: When a termination codon in a DNA molecule mutates into a codon encoding an amino acid, the synthesis of the polypeptide chain will not be terminated normally, and the peptide chain will continue to extend until it meets the next termination codon, thus forming an extended abnormal peptide chain. This mutation is called stop codon mutation and belongs to an extension mutation.
In addition, it also inhibits gene mutation. If different bases in different positions in a gene mutate respectively, so that one mutation inhibits the genetic effect of another mutation, this mutation is called inhibitory gene mutation.
(2) Frame shift mutation
Frame-shift mutation refers to the insertion or deletion of 1, 2 or more bases (but not 3 bases can be an integer multiple of 3) in the DNA chain, resulting in the corresponding changes in codon order and composition after the insertion or deletion of base sites. Due to the shift of the original codon, the stop codon often appears later or earlier, which leads to the extension or shortening of the newly synthesized peptide chain.
(3) Full-code mutation: If one or several codons are inserted or deleted between the codons of the DNA chain, the synthesized peptide chain will increase or decrease one or several amino acids, but the amino acid sequence before and after the "zero" or deletion site remains unchanged. This mutation is a complete coding mutation, also known as codon insertion or deletion.
2. Factors inducing gene mutation and its mechanism
(1) Physical mutation factors: All kinds of rays, such as X-ray, γ-ray, α-ray, β-ray and neutron, can induce gene mutation. When this kind of ray radiation acts on organisms, electrons are first knocked out from the outer layers of atoms or molecules of various substances in cells, causing ionization and excitation of atoms or molecules of these substances. When the chromosome or DNA molecule in a cell is excited by radiation ionization, its structure will change, which is the direct effect of ionizing radiation. Ionizing radiation has cumulative effect, and the mutagenic effect of low-dose long-term irradiation is the same as that of high-dose short-term irradiation.
(2) Chemical mutagenic factors: Some chemicals can cause gene mutation in organisms like radiation. There are three kinds: one is a mutagen that can change the chemical structure of DNA, such as nitrite and alkylating agent; One is the base analogue, whose molecular structure is very similar to the base in DNA molecule. When DNA molecules are copied, these base analogues can be added to DNA molecules as components of DNA, thus causing gene mutation. Common base analogues are 5- bromouracil and 2- aminopurine. There is also an acridine compound that can be inserted into the structure of DNA molecules, causing errors in the replication or transcription of DNA molecules and leading to mutations.
(3) Viral mutagenic factors: Some viruses can interfere with the normal DNA replication of the host cell and cause gene mutation after entering the host cell.
3. Characteristics and significance of gene mutation
(1) Universality refers to the universal existence of gene mutation in biology. The diversity of genes leads to the diversity of species, structures and characters of natural organisms, and genes may mutate under certain conditions. Among them, gene mutation under natural conditions is called natural mutation, and gene mutation induced under artificial conditions is called induced mutation.
(2) Randomness Because gene mutation occurs in the process of DNA replication, and most organisms have DNA, in the process of individual development, cell division and DNA replication are carried out at any time, and mutations may occur at any time as long as conditions change. If genetic mutation occurs in somatic cells, it cannot be passed on to offspring; if it occurs in germ cells, it can be passed on directly to offspring through fertilization.
(3) The same gene can mutate in different directions, resulting in a series of different alleles, that is, multiple alleles. When it is mutated, it can be mutated back to the original gene again.
(4) Low frequency Because the molecular structure of DNA in organisms is relatively stable, and DNA replication generally strictly follows the principle of base complementary pairing, the probability of gene mutation is very low.
(5) The disadvantages outweigh the advantages, because any living thing is the product of long-term natural selection, and they have reached a high degree of coordination with environmental conditions; If genetic mutation occurs, it may destroy this relationship and is often harmful to the survival of organisms.
Significance: Gene mutation is of great significance to biological evolution. It is the fundamental source of biological variation and provides the latest raw materials for biological evolution. Because there is no gene mutation, there will be no allele and no gene recombination. The internal cause of biological evolution is heredity and variation.
4. Gene recombination and its significance
Broadly speaking, any gene exchange process that causes genotype changes is called gene recombination. In a narrow sense, gene recombination only refers to gene communication involving DNA intramolecular fragmentation-recombination. In the process of meiosis, eukaryotes form various gametes through the free combination of non-homologous chromosomes, and male and female gametes combine to produce offspring with different genotypes. Although this recombination process will also lead to the change of genotype, it is not included in the narrow sense of gene recombination because it does not involve the intramolecular fragmentation and recombination of DNA.
Significance: it is one of the important reasons for biodiversity; It provides an extremely rich source for biological variation and is of great significance to biological evolution.
5. Comparison between gene recombination and gene mutation
Gene mutation, the essence of gene recombination
The molecular structure of genes has changed, resulting in new genes and the recombination of different genes with new characters. Instead of producing a new gene, a new genotype was produced, and the time and reason for its character recombination occurred. In the process of DNA molecular replication during interphase, due to the substitution, addition or deletion of base pairs caused by external physical and chemical factors or their own physiological factors, non-sister chromatids of homologous chromosomes cross-exchange during the first meiosis. As well as the interaction between the drastic changes of external conditions and internal factors under the condition of free combination of genes on non-homologous chromosomes, hybridization between different individuals is the fundamental source of biological variation in the process of sexual reproduction, the raw material of biological evolution, and also an important factor of biological variation. New excellent varieties can be cultivated through the recombination of cross breeding traits, and the frequency of possible mutation is low, but it is very common in sexual reproduction. 6. Chromosome structural variation and its types include deletion, repetition, inversion and translocation. Deletion refers to a segment deletion, middle deletion and top deletion of chromosomes and their genes. The genetic effect caused by deletion varies with the size of the deleted fragment and the developmental stage of the cell. In the individual development, the earlier the loss occurs, the greater the impact, the greater the impact on the individual, which will lead to the death of the individual and affect the vitality of the individual. In human inheritance, chromosome deletion often leads to more serious genetic diseases, such as meow syndrome. The phenomenon of variation caused by adding the same fragment to repeated chromosomes is called replication. But if the repeated part is too big, it will also affect the vitality of the individual and even cause the death of the individual. For example, the variation of Drosophila from normal oval eyes to rod eyes is the result of the repetition of a fragment on the X chromosome. Inverted chromosomes break at two points, resulting in three segments. The middle segment is inverted 180, which rejoins the other two segments and causes variation, which is called inversion. For example, there are three genes on chromosome 3 of Drosophila melanogaster, arranged in the order of scarlet eye-peach eye-triangle vein (ST-P-DL); The sequence of these three genes in another fruit fly is ST-DL-P, and this inversion alone constitutes the difference between the two species. Translocation refers to the phenomenon that a fragment of one chromosome is transferred to another non-homologous chromosome, thus causing variation. It is common for two non-homologous chromosomes to exchange fragments with each other, which is called mutual translocation. The genetic effect of mutual translocation is mainly to produce some abnormal gametes, which will reduce the fertility of gametes or produce offspring with genetic diseases. For example, chronic myeloid leukemia is caused by human chromosome 22 and 14 translocation. Translocation plays an important role in biological evolution. For example, in seed plants belonging to 29 genera of 17 family, there are types of variation caused by translocation, and nearly 100 varieties of Datura stramonium are the result of different chromosome translocation.
① A genome does not contain homologous chromosomes; (2) The chromosomes contained in a genome are different in shape, size and function; ③ A genome contains a set of genes that control a biological trait, but it cannot be repeated.
(2) Comparison between haploid and polyploid
The concept of haploid polyploidy: Individuals with gamete chromosomes of this species in somatic cells are developed from fertilized eggs, and individuals with three or more chromosomes in somatic cells are naturally formed due to the development of unfertilized eggs. Due to the drastic changes in natural conditions, the mitosis process is blocked and the number of chromosomes in the nucleus doubles. Meiosis forms germ cells with twice the number of chromosomes, and then fertilized to form zygotes and develop into polyploids. Artificial induction method for retired anther culture. Germinated seeds or seedlings treated with colchicine are characterized by weak plants, highly sterile stems, relatively large leaves, fruits and seeds, increased contents of nutrients such as sugar and protein, but delayed development and decreased seed setting rate. When treated with colchicine, the number of chromosomes is doubled, which can quickly obtain pure plants, shorten the breeding period, improve the breeding efficiency, and select new polyploid varieties, such as triploid seedless watermelon and octoploid triticale. (3) Autopolyploids and Allopolyploids.
Autopolyploid refers to the genome added to somatic cells from the same species, that is, the original chromosome is doubled (such as tetraploid rice, seedless watermelon, etc.) Allopolyploid refers to polyploid (such as common hexaploid wheat, octoploid triticale, etc.). ) is formed by different chromosomes in somatic cells of different species or even different genera.
(4) Comparison between polyploid breeding and haploid breeding.
① polyploid breeding:
② Haploid breeding:
③ comparison:
The principle of haploid breeding in polyploid breeding is chromosome doubling, chromosome doubling and reduction, and then pure nine fingers are obtained. ) Common methods: After colchicine treatment of retired anthers of germinated seeds and seedlings, chromosome doubling is artificially induced, which has the advantages of large organs, increased yield and nutritional components, and obviously shortened breeding years. Disadvantages: it is suitable for plants, but it is difficult to carry out technology on animals. Cooperation with cross breeding is complicated. 8.
When colchicine acts on dividing cells, it can form spindles, so that chromosomes cannot move to the two poles of the cells, thus doubling the number of chromosomes in the cells. Cells with doubled chromosome numbers continue to divide and may develop into polyploid plants in the future. In this experiment, low temperature was used to induce the change of chromosome number, and the effect of low temperature was basically similar to colchicine. Compared with colchicine, low temperature conditions are easy to create and control, low cost, harmless to human body and easy to operate. However, only the increase of chromosome number can be observed by microscope, and the specific increase is not easy to determine.
9. Types and examples of genetic diseases
Examples of human genetic diseases are defined as: monogenic genetic diseases, dominant genetic diseases, recessive genetic diseases such as polydactyly and syndactyly caused by dominant pathogenic genes, polygenic genetic diseases such as albinism and ketonuria controlled by more than two pairs of alleles, chromosomal abnormalities such as essential hypertension, genetic diseases such as chromosomal abnormalities and 2 1 trisomy syndrome caused by chromosomal abnormalities.
10. Comparison of congenital diseases, familial diseases and hereditary diseases
Congenital diseases are not necessarily genetic diseases, and acquired diseases are not necessarily genetic diseases. The so-called congenital disease refers to the deformity or disease that has been formed before death. When a deformity or disease is caused by genetic internal factors, and the chromosomal abnormality or pathogenic gene has been expressed or formed before the birth of the fetus, this congenital disease is of course a genetic disease, such as syndactyly, congenital deafness's disease, albinism and congenital stupidity. However, in the process of fetal development, due to the accidental influence of environmental factors, fetal organs develop abnormally, which leads to changes in morphology and function, and also leads to congenital malformation or birth defects. For example, if the mother is infected with rubella virus in the first three months of pregnancy, the fetus will have congenital heart disease, which is not caused by the change of genetic material, but by the interference of environmental factors during the embryonic development. Although it is congenital, it is not a genetic disease.
Familial disease means that many members of a family have the same disease, that is, a certain disease has a family history. Among genetic diseases, dominant genetic diseases often show obvious familial tendency, such as polydactyly, multiple colonic polyps, vitamin D-resistant rickets and so on. However, genetic diseases do not necessarily have a family history. For example, recessive genetic disease, because the patient's parents are heterozygotes, so the phenotype is normal, in the family with this kind of genetic disease, the incidence rate is small, so the cases in the family are often sporadic, and it is difficult to show the familial tendency. If relatives are not married, there are often only a few patients in the offspring.
Familial diseases are not all genetic diseases. This is because many members of the same family may suffer from the same disease because of the same environmental factors. For example, many members of a family may suffer from night blindness due to lack of vitamin A in their diet.
1 1. Human genome project and human health
(1) human genome
Refers to all the genetic information carried by human DNA molecules. The human haploid genome consists of 23 double-stranded DNA molecules, with 3× 109 base pairs and an estimated 35,000 genes.
(2) Human Genome Project (HGP)
Study the human genome and analyze the deoxynucleotide sequence of the human genome, so as to interpret all the genetic codes and reveal all the mysteries of life.
(3) The main objectives of the Human Genome Project
Complete the sequencing of 3× 109 base pairs of human genome, and make clear the position, function, structure, expression regulation mode and all information of pathogenic mutations of all genes in human body.
Its main contents include drawing four maps of the human genome, namely, genetic map, physical map, sequence map and transcription map (countries participating in this project include the United States, Britain, Japan, France, Germany and China).
(4) Research on the Human Genome Project.
① Grouping of human genome. For example, it can be divided into 24 groups according to different chromosomes, and each chromosome can be divided into long arm region, short arm region, band and subband.
② Labeling the human genome refers to finding some specific DNA sequences for each chromosome or smaller region.
③ Sequencing the cloned genomic DNA with known marker sequences.
④ Cloning and determining the complete sequence of human genome.
⑤ To study the structure, function and expression regulation of each gene.
(5) China has joined the Human Genome Project.
1In September, 1999, the Human Genome Center of the Institute of Genetics of China Academy of Sciences and the North-South Center of the National Human Genome undertook the task of 1% international large-scale sequencing of the human genome. That is, the sequencing task of 30 million base pairs on the short arm of chromosome 3 from D3336 10 to the 30Mb region of telomere.
Among many human genes, people are most concerned about genes related to various diseases. It is estimated that there are about 5,000 genes related to human diseases. So far, 1500 genes related to human diseases have been isolated and confirmed. The breakthrough to decipher these genes is to obtain blood samples from families with genetic diseases, and then analyze and determine DNA. China, with 22% of the world's population and 56 ethnic groups and 206 ethnic relations, is a rare country with diverse genes. Due to backward economy and culture, long-term geographical isolation and narrow intermarriage, there are many families with hereditary diseases in China. Whoever gets the blood sample of the hereditary disease family first can get the patent first, thus monopolizing the future market of this bioengineering product. As a member of the Human Genome Project, China enjoys the advantages of resources, which will bring infinite economic benefits to the bioengineering industry in China in the future, especially the pharmaceutical industry.
(6) the significance of completing the human genome project
(1) can further deepen people's understanding of themselves and bring great influence to the whole life science and even the whole human society.
② An accurate understanding of the human genome is helpful to further study the regulation of human gene expression.
(3) Obtaining all human gene sequences will help people understand the pathogenesis of many hereditary diseases and cancers, provide theoretical basis for molecular diagnosis and gene therapy, help people understand the development process of human body and enhance human health.
④ It is of great significance to further understand the mechanism of growth, differentiation and individual development of human cells and the evolution of organisms.
⑤ The implementation of the Human Genome Project will promote the development of high-tech organisms and generate huge economic benefits.