Mutations are an important object of study for cytogeneticists and biochemists. It is mutations, gene or chromosomal, that are most often the cause of hereditary diseases. Under natural conditions, chromosomal rearrangements occur very rarely. Mutations caused by chemicals, biological mutagens, or physical factors such as ionizing radiation are often the cause of congenital malformations and malignancies.
General information about mutations
Hugh de Vries defined a mutation as a sudden change in a hereditary trait. This phenomenon is found in the genome of all living organisms, from bacteria to humans. Under normal conditions, mutations in nucleic acids occur very rarely, with a frequency of approximately 1 10–4 – 1 10–10.
Depending on the amount of genetic material affected by the changes, mutations are divided into genomic, chromosomal and gene. Genomic ones are associated with a change in the number of chromosomes (monosomy, trisomy, tetrasomy); chromosomal are associated with a change in the structure of individualchromosomes (deletions, duplications, translocations); gene mutations affect a single gene. If the mutation affected only one pair of nucleotides, then it is a point mutation.
Depending on the causes that caused them, spontaneous and induced mutations are distinguished.
Spontaneous mutations
Spontaneous mutations occur in the body under the influence of internal factors. Spontaneous mutations are considered normal, they rarely lead to serious consequences for the body. Most often, such rearrangements occur within the same gene, associated with the replacement of bases - purine for another purine (transition), or purine for pyrimidine (transversion).
Significantly less often spontaneous mutations occur in chromosomes. Chromosomal spontaneous mutations are usually represented by translocations (the transfer of one or more genes from one chromosome to another) and inversions (changes in the sequence of genes in a chromosome).
Induced rearrangements
Induced mutations occur in the body's cells under the influence of chemicals, radiation or virus replication material. Such mutations appear more often than spontaneous ones and have more serious consequences. They affect individual genes and groups of genes, blocking the synthesis of individual proteins. Induced mutations often globally affect the genome, it is under the influence of mutagens that abnormal chromosomes appear in the cell: isochromosomes, ring chromosomes, dicentrics.
Mutagens, in addition to chromosomal rearrangements, cause DNA damage: double-strand breaks,the formation of DNA crosslinks.
Examples of chemical mutagens
Chemical mutagens include nitrates, nitrites, nitrogen base analogs, nitrous acid, pesticides, hydroxylamine, some food additives.
Nitrous acid causes the amino group to be cleaved from nitrogenous bases and replaced by another group. This leads to point mutations. Hydroxylamine also causes chemically induced mutations.
Nitrates and nitrites in high doses increase the risk of cancer. Some nutritional supplements cause arylation reactions of nucleic acids, which leads to disruption of transcription and translation processes.
Chemical mutagens are very diverse. Often it is these substances that cause induced mutations in chromosomes.
Physical mutagens
Physical mutagens include ionizing radiation, primarily shortwave, and ultraviolet. Ultraviolet starts the process of lipid peroxidation in membranes, provokes the formation of various defects in DNA.
X-ray and gamma radiation provoke mutations at the level of chromosomes. Such cells are not capable of division, they die during apoptosis. Induced mutations can also affect individual genes. For example, blocking tumor suppressor genes leads to tumors.
Examples of induced rearrangements
Examples of induced mutations are various genetic diseases, which are more often manifested in areas prone toexposure to a physical or chemical mutagenic factor. It is known, in particular, that in the Indian state of Kerala, where the annual effective dose of ionizing radiation exceeds the norm by 10 times, the frequency of birth of children with Down syndrome (trisomy on the 21st chromosome) is increased. In the Chinese district of Yangjiang, a large amount of radioactive monazite was found in the soil. Unstable elements in its composition (cerium, thorium, uranium) decay with the release of gamma quanta. The impact of shortwave radiation on the residents of the district has led to a large number of births of children with crying cat syndrome (deletion of a large section of the 8th chromosome), as well as an increased incidence of cancer. Another example: in January 1987, a record number of births of children with Down syndrome was registered in Ukraine, associated with the Chernobyl accident. In the first trimester of pregnancy, the fetus is most sensitive to the effects of physical and chemical mutagens, so a colossal dose of radiation has led to an increase in the frequency of chromosome anomalies.
One of the most infamous chemical mutagens in history is the sedative Thalidomide, manufactured in Germany in the 1950s. Taking this drug has led to the birth of many children with a wide variety of genetic abnormalities.
The induced mutation method is commonly used by scientists to find the best way to fight autoimmune diseases and genetic abnormalities associated with protein hypersecretion.
