-gene mutation in the new form

(College of Zoology X X X in 2005)

Abstract: Chromosome: 1, the structure of chromosome is in the metaphase of mitosis, and each chromosome has two chromatids, which are called sister chromosomes. The two monomers are connected by centromere, and the depression at the centromere becomes narrower, which is called primary constriction. Centromeres divide chromosomes into short arms (P) and long arms (Q). At the ends of short and long arms, there is a special site called telomere. On the long and short arms of some chromosomes, there are also depressed and narrowed parts, which are called secondary constriction marks. There is a spherical structure at the end of the short arm of human proximal centromere chromosome, which is called satellite. 2. Chromosome types Human chromosomes are divided into three types: metacentric chromosomes, metacentric chromosomes and proximal centromeric chromosomes. 3. Chromosome number The chromosome number of human somatic cells (diploid cells, 2n) is 46 (23 pairs, 2n=46), of which 22 pairs are autosomes and 1 pair is sex chromosomes (the two sex chromosomes of women are XX chromosomes with the same morphology; Men have only one X chromosome and the other is the smaller Y chromosome); Normal germ cells (haploid cells, n) have 23 chromosomes (n=23).

Keywords: heredity; Variation; gene mutation

Heredity is a similar phenomenon between parents and children, that is, as the saying goes, "As you sow, you reap". Its essence is that organisms obtain substances from the environment according to their parents' development methods and ways, and produce copies similar to their parents. Inheritance is relatively stable, and organisms will not easily change the development path and mode inherited from their parents. Therefore, parents' looks, behavior habits and excellent personality can be reproduced in future generations, even resembling their parents. Parents' defects and genetic diseases will also be passed on to future generations.

Inheritance is the basic attribute of all living things, which keeps the biological world relatively stable and enables human beings to know the biological world including themselves.

Variation refers to the differences between parents and children, siblings and individuals of the same species. As the saying goes, "One mother gives birth to nine children, and nine children are different." There are no two absolutely identical individuals in the world, including twins, which fully shows that genetic stability is relative and variation is absolute.

Inheritance and variation of organisms are two sides of the same thing. Heredity can vary, and variation can be inherited. A normal and healthy father can give birth to children with genetic defects in intelligence and physique, and pass on genetic defects (mutations) to the next generation.

The material basis of heredity and variation Whether the inheritance and variation of organisms have a material basis has been debated in the field of genetics for decades. In the field of modern biology, it is recognized that the genetic materials of organisms are chromosomes at the cellular level and genes at the molecular level, and their chemical components are deoxyribonucleic acid (DNA). In a few prokaryotes without DNA, such as tobacco mosaic virus, RNA is genetic material.

Eukaryotic cells have intact nuclei and many organelles in the cytoplasm. The genetic material of eukaryotes is chromosomes in the nucleus. However, the cytoplasm also shows certain genetic functions in some aspects. The material connection between human parents and their offspring is sperm and eggs, and the material with genetic function in sperm and eggs is chromosomes. According to the genetic information contained in DNA in chromosomes, fertilized eggs develop into offspring similar to their parents.

First of all, the mystery of heredity and variation

As the saying goes, "As you sow, you reap", which is the fundamental feature of biological inheritance. Humans, like other creatures, always retain some basic characteristics of their parents in the alternation of generations, which is called heredity. But future generations will be different from their parents, and some differences are still obvious. What is the difference between offspring and parents? Smart? Blame? Huh? What is the basis of Huai Mu's life?

Hereditary and heritable variation are determined by genetic material. This genetic material is the gene in the cell chromosome. Like most living things, human chromosomes are composed of DNA (deoxyribonucleic acid) chains, and genes are specific fragments of DNA chains. Because parental chromosomes are passed on to offspring through reproductive process, this produces heredity. In the process of life or reproduction, chromosomes may also be distorted, and mutations may occur within genes, which may lead to variation.

For example, genetics points out that the daughter of a color-blind father generally does not show color blindness, but she obtained the color-blind gene of her parents, and her son will also suffer from color blindness in the next generation because of obtaining the color-blind gene.

We observe many biological species around us: animals, plants, microorganisms and humans. Although there are many kinds, after many years, people are still people, chickens or chickens, dogs or dogs, ants, elephants, peach trees, willows and various flowers and plants, and so on. Thousands of creatures in Qian Qian can still maintain their own characteristics, including morphological structure and physiological function. It is precisely because of this genetic characteristic of the biological world that all kinds of creatures in nature can survive and live in an orderly way and reproduce.

You may ask, creatures are handed down from generation to generation, and the morphological structure and physiological function of each creature should be exactly the same, but why do children born to parents have their own characteristics? For another example, different people's skin or kidneys are transplanted to each other, and rejection will occur, which is unacceptable to each other. How do you explain this? Scientists' research results tell us that in addition to genetic phenomena, there are also variation phenomena in the biological world, that is to say, there are differences between individuals. For example, it is not uncommon for children born to a couple to have different appearances. Ugly parents give birth to beautiful children, and mediocre parents give birth to smart children. I'm afraid it's hard to find two identical people in the world. Even identical twins look exactly the same to outsiders, but their parents who live with them day and night can distinguish the subtle differences between them. This phenomenon is mutation. Most human variations are caused by different combinations of parents' genetic genes. Each child gets half the genes from his father and the other half from his mother. Although each child gets the same number of genes, but the content is different, so each child is a new combination, different from parents and siblings, thus forming the differences between them. It is precisely because of variation that human beings have many nationalities. People can easily recognize Zhang San and Li Si from the crowd. If there is no variation, everyone is the same, and there will be more trouble in society. Variation includes not only the differences in appearance, but also the basic substance that constitutes the body-protein also has variation, and everyone has his own unique protein. Therefore, if skin or organs are transplanted from one person to another, rejection will occur, because the protein between them is different.

Another kind of mutation is gene mutation, which is often induced by environmental conditions. This mutated gene can be passed on to the next generation. Many gene mutations can lead to genetic diseases.

Variation may also be caused entirely by environmental factors, such as limping after polio and dementia after encephalitis. These traits are caused by environmental factors, because virus infection damages some tissues, resulting in abnormal physiological function, not genetic material changes, so it is not a genetic problem, so it will not be passed on to the next generation.

In a word, heredity and variation are two inseparable aspects of genetic phenomena. We have genetic material from our parents to ensure that our basic human characteristics will remain unchanged for a long time. In the process of inheritance, variation constantly occurs, and everyone develops and grows in a certain environment, which leads to the diversity of human beings.

Second, the scientific theory of genetic variation

1. 1 Molecular basis of heredity

(a) Existing forms of genetic material

(1) chromosome is the carrier of genetic material, and genetic information is contained in DNA molecules in the form of genes.

(2) Each human cell contains two genomes, and the DNA of each genome constitutes one genome;

(3) Genome in a broad sense includes nuclear chromosome genome and mitochondrial genome;

(4) About 90% of human nuclear chromosome genome is DNA repetitive sequence, and 10% is single sequence;

(5) Polygene family is one of the important structures in eukaryotic genome.

(b) the structure and function of genes

1.2, molecular structure of eukaryotic gene

(1), the DNA sequence of the gene consists of coding sequence and non-coding sequence. The coding sequence is discontinuous and separated by non-coding sequences, forming a mosaic-arranged broken form, so it is called a broken gene; The coding sequence is called exon and the non-coding sequence is called intron.

(2) There is a highly conserved sequence in the junction region between each exon and intron, which is called exon-intron junction, that is, the two nucleosides at the 5' end of each intron are GT and the 3' end is AG, which is called GT-AG rule;

(3) The size of eukaryotic genes varies greatly, and the relationship between exons and introns is not fixed;

(Of the two strands of DNA molecules, the 5'→3' strand is called the coding strand, and its base sequence stores genetic information; The 3'→5' strand is called the anti-coding strand, which is the template of RNA synthesis.

(5) There is a non-coding region outside the first exon and the last exon of each broken gene, which is called flanking sequence, and there are a series of regulatory sequences on it, which play a regulatory role in gene expression. These structures include:

① Promoter: located at the starting point of gene transcription, it is the binding site of RNA polymerase and can start gene transcription.

② Enhancer: located upstream or downstream of the gene transcription start point, it can enhance the transcription of the promoter and improve the transcription efficiency;

③ Terminator: A sequence located downstream of the 3' non-coding region, which provides a transcription termination signal in transcription.

1.3, gene replication

(1), gene replication is based on DNA replication, and each DNA molecule has multiple replication units (replicators);

(2) Each replicator has a replication starting point, from which two-way replication starts, and replication fork is formed on both sides of the starting point;

(3) DNA polymerase can only add deoxynucleoside nucleus at the 3' end of DNA chain, so replication can only be carried out in the direction of 5'→3';

(4) The new chain in the same direction as replication fork replicates continuously and rapidly, which is called the leading chain; Contrary to replication fork, the replication of the new strand is discontinuous (Okazaki fragment must be synthesized in the presence of RNA primers, and then a piece of DNA is added under the action of DNA ligase), and the speed is also slow, which is called downlink; Therefore, DNA replication is semi-intermittent replication;

(5) Replicated DNA molecules all contain an old strand and a new strand, so DNA replication is semi-conservative.

1.4, gene expression

Gene expression is a process in which the genetic information contained in DNA molecules forms a biologically active protein through transcription and translation, or functions through transcribed RNA.

(1), transcription: It is the process of synthesizing RNA with DNA as a template under the catalysis of RNA polymerase.

① The newly synthesized RNA is called heteronuclear RNA (also called heteronuclear RNA, HNRNA);

②hnRNA can only form mature mRNA through the processes of "capping", "tailing" and splicing.

(2) Translation: Using mRNA as a template to guide the process of protein synthesis.

① Every three adjacent bases in the ①mRNA molecule are triplets, and one amino acid can be determined, which is called codon;

② Most of the initial products after translation have no function and need to be further processed into protein with certain activity.

1.5, Regulation of Gene Expression (Understanding Operon Theory)

1.6, gene mutation

(1), the concept of gene mutation: A gene mutation is a change in the nucleotide sequence of a DNA molecule, which leads to a change in the coding information of the genetic code, a change in the amino acid of the gene expression product protein, and thus a change in the phenotype.

(2) the way of gene mutation

① Base substitution is also called point mutation, including transformation and transversion. Its consequences can cause synonymous mutation, missense mutation, nonsense mutation or termination mutation (prolonged mutation) and other biological effects.

(2) frameshift mutation refers to the increase or decrease of one or several base pairs at a certain site in a DNA molecule, which leads to the change of all genetic coding information after that site.

③ When dynamically mutated microsatellite DNA or short tandem repeats, especially trinucleotide repeats, are close to or located in the gene sequence, the number of repeats will obviously increase from generation to generation, leading to the occurrence of some hereditary diseases.

(3) the repair of gene mutation

① Resection and repair is a multi-step enzymatic reaction process. First, the damaged DNA site is excised, and then a fragment is synthesized and connected to the excised site to repair the damage.

② Recombination repair, also called post-replication repair, refers to that after DNA is damaged and thymine dimer (T-T) is produced, when DNA is copied to the damaged site, a gap appears at the site corresponding to T-T, resulting in a breakpoint on the complete DNA chain. At this time, under the action of recombinant protein, the complete mother chain is recombined with the recombinant sub-chain, and the nucleotide fragment of the mother chain supplements the deletion on the sub-chain. Under the action of DNA polymerase, a single-stranded DNA fragment is synthesized to fill the incision of the recombinant mother chain, and then the new fragment is connected with the old chain through phosphodiester bond under the action of DNA ligase, thus completing the repair process.

2. The cellular basis of heredity

Chromatin: In interphase nuclei, chromatin has different functional states and different folding degrees, which can be divided into euchromatin and heterochromatin. 1, euchromatin is in an uncoiled state during intercellular period, with transcriptional activity, loose and shallow staining; 2. Heterochromatin is concentrated in intercellular phase, with little or no transcription activity and deep staining; 3. Sex chromatin shows a special structure in the heterochromatin part of interphase nuclear chromosomes. There are two kinds: (1). In the interphase nucleus of women with normal X chromatin, there is a dark stained oval body with a size of about 65438 00 nm (understanding Lyon hypothesis). (2) After the interphase nuclei of men with normal Y chromatin were stained with fluorescent dyes, round or oval strong fluorescent corpuscles with a diameter of about 3nm could be seen in the nuclei.

Chromosome: 1. Chromosome structure in the metaphase of mitosis, each chromosome has two chromatids, which are called sister chromosomes. The two monomers are connected by centromere, and the depression at the centromere becomes narrower, which is called primary constriction. Centromeres divide chromosomes into short arms (P) and long arms (Q). At the ends of short and long arms, there is a special site called telomere. On the long and short arms of some chromosomes, there are also depressed and narrowed parts, which are called secondary constriction marks. There is a spherical structure at the end of the short arm of human proximal centromere chromosome, which is called satellite. 2. Chromosome types Human chromosomes are divided into three types: metacentric chromosomes, metacentric chromosomes and proximal centromeric chromosomes. 3. Chromosome number The chromosome number of human somatic cells (diploid cells, 2n) is 46 (23 pairs, 2n=46), of which 22 pairs are autosomes and 1 pair is sex chromosomes (the two sex chromosomes of women are XX chromosomes with the same morphology; Men have only one X chromosome and the other is the smaller Y chromosome); Normal germ cells (haploid cells, n) have 23 chromosomes (n=23).

(3) Normal human karyotype: The analysis of chromosome number and morphological structure features is called karyotype analysis. 1. Non-banding karyotype According to Denver system, 46 chromosomes of normal human cells are divided into 23 pairs and 7 groups (groups A, B, C, D, E, F and G). When describing the karyotype, first write down the total number of chromosomes (including sex chromosomes), then the number ","and finally the sex chromosomes. The normal male karyotype is described as 46, xy; Female 46, XX. 2. banding karyotype uses various special staining methods, and the chromosomes are bright and dark or bright and dark bands along the long axis, so it is also called banding. According to ISCN regulations, when describing a specific band, four items need to be specified: ① chromosome number; ② number of arms; ③ Area code; 4 number.

Basic laws of heredity: Mendel's law of free combination of separation phenomena and Morgan's law of chain exchange constitute the basic laws of heredity, which are generally called the three laws of heredity. Separation phenomenon said that there are obvious recessive differences in genetic traits, so a pair of traits with obvious recessive differences are called relative traits. Dominant traits in relative traits are controlled by dominant genes, while recessive traits are determined by a pair of homozygous recessive genes. Heterozygotes often show the characteristics of dominant genes. Genes exist in pairs in somatic cells. When they form gametes, they will separate from each other and enter different daughter cells. During meiosis, homologous chromosomes separate from each other and enter different germ cells, which is the cytological basis of the separation law. The law of free combination means that when organisms form gametes, different pairs of genes act independently, can be separated and combined, and can be combined into the same gamete with equal opportunities. The random combination of non-homologous chromosomes during meiosis of germ cells is the cytological basis of the law of free combination. Linkage exchange law means that genes located on the same chromosome are linked with each other, and they are often transmitted together (linkage law), but sometimes separation and recombination occur because pairs of alleles on homologous chromosomes are exchanged. In meiosis, the association and exchange of homologous chromosomes is the cytological basis of the exchange law.

Inheritance of monogenic traits: if a genetic trait is controlled by a pair of genes, it is called inheritance of monogenic traits. Monogenic traits are also called quality traits. 1, the allele that determines a certain genetic trait obeys separation phenomenon when transmitted; 2. When the genes that determine two genetic traits are located on different pairs of chromosomes, the transmission of these two monogenic traits conforms to the law of free combination. 3. If the genes that determine two genetic traits are located on the same pair of chromosomes, their transmission will obey the law of chain exchange.

Inheritance of polygenic traits: traits controlled by polygenes are often different from monogenic traits, and their variation is often continuous quantitative variation, which is called quantitative traits. Each pair of genes has little effect on the formation of polygenic traits, which is called minor genes. The effects of micro-genes are often cumulative. Polygenic genetic traits are not only influenced by polygenic genetic basis, but also by environmental factors. (Familiar with polygenic inheritance hypothesis and understand the characteristics of polygenic inheritance)

Genetic variation: (1) chromosomal abnormalities and diseases; Chromosome abnormality class; Forming machine;

Digital distortion

Aneuploid change

monoploid

Polyploid polyploid polyploid polyploid

Bisexual fertilization, bisexual fertilization, nuclear replication

Aneuploid change

Subdoubled

Chromosomes are not separated, and chromosomes are lost.

Hyperdiploid

malformation

Del (missing)

Affected by many factors, such as physical factors, chemical factors, biological factors and so on.

repeat

Inversion (inv)

translocation

Ring chromosome

Dicentric chromosome

isochromosome

1. A cell line with two or more karyotypes exists in an individual, and this individual is called a chimera.

2. There are two ways to describe chromosome structural aberration: simple and detailed.

(2) Monogenic genetic diseases 1 and autosomal dominant genetic (AD) diseases in humans.

(1) and the characteristics of AD families: ① The pathogenic gene is located on the autosome, and the inheritance has nothing to do with sex; ② At least one parent is a patient, but most of them are heterozygotes; ③ If the patient marries a normal individual, the risk of offspring is1/2; ④ Continuous transmission can be seen on the pedigree.

(2) Other types of AD: ① Incomplete dominance or semi-dominance means that the phenotype of heterozygote is between dominant homozygote and recessive homozygote; (2) Irregular dominance means that heterozygotes do not necessarily show corresponding symptoms for some reason, even if they are sick, the degree of illness is different; (3) * * * dominance means that a pair of alleles are not recessive, and the functions of both genes can be expressed in the state of heterozygosity; (4) Delayed dominance, heterozygotes with dominant pathogenic genes do not show corresponding symptoms in the early life, and their functions will not be shown until a certain age.

2. Autosomal recessive genetic diseases

The characteristics of (1) and AR families are as follows: ① The inheritance of pathogenic genes has nothing to do with sex, and the incidence of diseases is equal between men and women; ② Parents of patients often have normal phenotype, but they are all carriers of pathogenic genes. About 65,438+0/4 of the patients may be sick, 3/4 have normal phenotype, but 2/3 of those with normal phenotype are possible carriers. ③ There is no continuous transmission phenomenon in the genealogy, and it is often sporadic; ④ The incidence of inbreeding offspring is higher than that of non-inbreeding offspring.

(2) Common AR diseases: phenylketonuria, albinism, congenital deafness's disease, high myopia and sickle cell anemia.

3.x-linked dominant genetic diseases

The characteristics of (1) and XD families are as follows: ① There are more female patients than male patients in the family, and the female patients are less ill; ② At least one parent of the patient is a patient; ③ Among the descendants of male patients, all daughters are patients and all sons are normal; In the offspring of female patients, the risk of each child is1/2; ④ Continuous transmission can be seen on the pedigree.

(2) Common XD disease: vitamin D-resistant rickets.

4.x-linked recessive genetic diseases

Characteristics of (1) and XR families: ① There are far more male patients than female patients in the population; (2) When the parents are not sick, the son may get sick and the daughter will not get sick; ③ Because of cross-inheritance, the brothers, uncles, cousins and nephews of patients each have the risk of 1/2; If a woman is a patient, then her father must be a patient and her mother must be a carrier or a patient.

(2) Common XR diseases: hemophilia A and red-green color blindness.

5.y- linked genetic (YL) diseases are inherited by all men.

(3) Polygenic genetic diseases

1. Some important concepts about polygenic genetic diseases

(1), the susceptibility to polygenic diseases, and the risk of polygenic diseases are determined by polygenic genetic basis.

(2) Susceptibility depends on genetic basis and environmental factors, which determines whether an individual is susceptible to illness.

(3), onset threshold When the individual's susceptibility reaches a certain level, that is, reaches a limit, the individual will get sick, and this limit of susceptibility is called the threshold.

(4) Heritability In polygenic genetic diseases, susceptibility is influenced by both genetic basis and environmental factors, and the degree of the role played by genetic basis is called heritability or heritability. Generally expressed as a percentage (%).

2. Characteristics of polygenic genetic diseases

(1), there is a trend of family aggregation, and the incidence of relatives of patients is higher than that of groups;

(2) With the decrease of the level of relatives, the risk of illness of patients' relatives decreased rapidly;

(3) The risk of children's illness increases when close relatives get married;

(4) There are racial (or ethnic) differences in the incidence.

Third, contemporary inheritance and variation.

The draft of the Human Genome Project was completed on June 26th this year, but it will take some time to complete the assembly of all 3 billion bases, which is expected to be in June next year. Even if the "fine map" of the human genome project is completed, it is only the beginning for us to understand the function of human genes. It will take at least 40 years to fully understand the functions of genes and their interactions. Needless to say, this is a huge project.

Up to now, there is still controversy about the number of genes contained in the whole human genome. Some people say it's 30,000, while others say it's 654.38+0.4 million, which is quite different. In the whole human genome sequence, there is only 1% difference, which leads to differences in race, skin color, height, eyes, obesity and susceptibility to diseases. In addition to continuing to study the quantity and function of genes, to what extent genes are influenced by external environment and internal factors and whether this change can be passed down from generation to generation is also a problem to be solved.

The above problems involve the category of epigenetics. Post-formation theory is a science to study the semi-permanent changes of gene activity through other chemical channels, rather than the usual base mutation. The importance of the late success theory has always been controversial. If there is a scientific basis, it will be the key to explain the differences between different individuals and even different species, and it will also be an important mechanism for the occurrence of diseases.

Expression of different genes: Genes contain instructions to synthesize protein, and the process of protein synthesis is called gene expression. However, geneticists have long known that the modification of chemical groups on DNA bases can regulate gene expression and affect the synthesis of protein. The most common modification method is gene methylation (methyl is a group consisting of one carbon atom and three hydrogen atoms), that is, adding methyl groups to genes often terminates gene expression.

Through the study of some mammals, the researchers found that this modification only exists in individuals and will not be passed on to future generations, because this modification is often removed in sperm and egg cells. Recently, it has been found that the formed characteristics can be inherited in mice. In the experiment made by Dr. whitelaw, a chemist at the University of Sydney, mice with the same genes are more like their mothers than their parents. Because they inherit the methylation type of mother's egg DNA. This type of methylation plays a very important role in determining the coat color of mice.

A great deal of research data from Dr. whitelaw's team show that it is necessary to find out the heritable epigenetic characteristics before finding out how animals pass on their physical characteristics or disease susceptibility to their offspring. If epigenetic characteristics can be inherited, then the diseases caused by these characteristics should be transmitted from family to family like ordinary genetic mutations. The research team conducted an in-depth study on how to turn off and express post-formation markers in mice during passage. The researchers introduced a gene (called transgene) that can produce a specific type of red blood cells into the genome of mice with the same genetic characteristics (mice receiving the gene are called transgenic mice). It was found that the transgenes in these transgenic mice were expressed in different ways. Some transgenic mice express this gene in 40% of red blood cells, while others do not express it at all. At the same time, the team also studied the coat color of mice and found that the increase of DNA methylation related to coat color was related to the non-expression (or "silent" expression) of transgenes. However, in this case, the acquired change may come from parents or parents.

It is puzzling that although the silence of gene expression can last for at least three generations, it is not irreversible. When this type of offspring mice mated with non-similar mice, it was found that there was no methylation and expression silence in the offspring mice, and the transgene could be expressed in the young mice. If this phenomenon of gene silencing and reactivation occurs naturally, it can explain the differences between individuals and generations.

The theory of offspring can also explain the differences between species. Recently, Dilg Mann of Princeton University destroyed the genetic characteristics of several mice by mating two similar mice. These mice can't mate normally, and their hybrid offspring show abnormal growth. Researchers believe that this abnormal growth is related to the destruction of methylation patterns in hybrid offspring genes. They speculate that the epigenetic effect is very significant, and only by changing these characteristics can new species be created.

As we all know, the generation of species is the result of gradual accumulation of genetic variation. However, Dilg Mann believes that the rapid emergence of some species cannot be explained by this hypothesis. Therefore, the postemergence hypothesis has certain advantages. For example, methylation can quickly shut down the expression of the whole gene and cause fundamental changes. This change is enough to prevent new varieties from crossing with old varieties, especially to prevent the emergence of new varieties.

Four. conclusion

Expression of mutant genes: Many biologists despise this hypothesis. Although the gene sequence can not fully explain the characteristics of animals, it can at least explain some diseases caused by gene mutation.

Advocates of the disease gene mutation hypothesis take cancer as a classic example to illustrate how many base errors at the individual DNA level can lead to tumors. However, Dr. Dusberg of the University of California, Berkeley disagrees with this view. He thinks that cancer is not caused by genetic abnormality, but by another form of post-emergence chromosomal abnormality.

According to the hypothesis of cancer gene mutation, the gene mutation that leads to cell division and death destroys the normal process of cell division and death, leading to cell growth out of control. Recently, however, a research team led by Dr. Dusberg reported that so far, no one has confirmed that mutated genes can turn normal cells into cancer cells. He also pointed out that if the mutant gene has a significant effect on cell division, it is very strange why in some cases, the mutation will develop into cancer after months or even years. He believes that the above problems can be explained by the phenomenon of anaplastic aneuploidy, which means that the number of chromosomes in cells is wrong.

During cell division, chromosomes are arranged neatly and distributed to daughter cells through spindle (a kind of scaffold of protein). Dusberg speculated that carcinogenic chemicals can affect the spindle, resulting in daughter cells with more or less chromosomes. Because of the instability of this mismatched chromosome, chromosomes mix with each other during cell division, resulting in unnatural recombination.

Most recombination is essential for cells, but it will eventually produce a cell with abnormal division. The probability of producing such abnormal cells is very small, and this low probability event can explain why it takes so long from exposure to carcinogens to cell canceration. Cell aneuploidy is a remarkable feature of more than 5000 kinds of tumors.

Compared with individual base mutation, the increase or decrease of chromosome number makes the cell characterization change significantly. Because the change of chromosome number (that is, aneuploidy) will lead to the change of thousands of protein activities, not just one or two kinds of protein, leading to cell division out of control. If this hypothesis holds, then the strategy of trying to treat cancer by fixed-point repair of oncogenes is ineffective.

Dr. Dusberg is notorious for his hypothesis 10 years ago. He believes that human immunodeficiency virus will not cause AIDS. A series of studies on HIV and AIDS show that Dusberg's theory is extremely absurd. This has seriously damaged his reputation, so his other theories are easily ignored. However, his aneuploidy hypothesis seems to be very valuable. The universality of aneuploidy in cancer needs to be further clarified.