What mutations are called spontaneous? If we translate the term into an accessible language, then these are natural errors that occur in the process of interaction of genetic material with the internal and / or external environment. Such mutations are usually random. They are observed in the genital and other cells of the body.
Exogenous causes of mutations
Spontaneous mutation can occur under the influence of chemicals, radiation, high or low temperatures, rarefied air or high pressure.
Every year, on average, a person absorbs about one-tenth of a rad of ionizing radiation that makes up the natural background radiation. This number includes gamma radiation from the Earth's core, the solar wind, and the radioactivity of elements found in the thickness of the earth's crust and dissolved in the atmosphere. The dose received also depends on where the person is located. A quarter of all spontaneous mutations happen due to this factor.
UV radiation, contrary to popular belief, plays a minor role inthe occurrence of DNA breakdowns, as it cannot penetrate deep enough into the human body. But the skin often suffers from excessive sun exposure (melanoma and other cancers). However, single-celled organisms and viruses mutate when exposed to sunlight.
Too high or low temperatures can also cause changes in the genetic material.
Endogenous causes of mutations
The main reasons why spontaneous mutation can occur remain endogenous factors. These include metabolic by-products, errors in the process of replication, repair or recombination, and others.
-
Failures in replication:
- spontaneous transitions and inversions of nitrogenous bases;
- incorrect insertion of nucleotides due to errors in DNA polymerases;- chemical replacement of nucleotides, for example, guanine-cytosine to adenine-guanine.
- Restoration errors:- mutations in the genes responsible for the repair of individual sections of the DNA chain after they break under the influence of external factors.
- Problems with recombination:- failures in the processes of crossing over during meiosis or mitosis lead to loss and completion of bases.
These are the main factors that cause spontaneous mutations. The reasons for failures may be the activation of mutator genes, as well as the conversion of safe chemical compounds into more active metabolites that affect the cell nucleus. In addition, there are also structural factors. These include repeats of the nucleotide sequence near the sitechain rearrangements, the presence of additional DNA sections similar in structure to the gene, as well as mobile elements of the genome.
Pathogenesis of mutation
Spontaneous mutation occurs as a result of the impact of all of the above factors acting together or separately in a certain period of the cell's life. There is such a phenomenon as a sliding violation of the pairing of the daughter and maternal DNA strands. As a result, loops are often formed from peptides that have not been able to fit into the sequence adequately. After the removal of excess DNA fragments from the daughter strand, the loops can both be resected (deletions) and built in (duplications, insertions). The changes that have appeared are fixed in the next cycles of cell division.
The rate and number of mutations that occur depend on the primary structure of DNA. Some scientists believe that absolutely all DNA sequences are mutagenic if they form bends.
Most common spontaneous mutations
What is the most common manifestation of spontaneous mutations in the genetic material? Examples of such conditions are the loss of nitrogenous bases and the removal of amino acids. Cytosine residues are considered especially sensitive to them.
It has been proven that today more than half of vertebrates have a mutation of cytosine residues. After deamination, methylcytosine changes to thymine. Subsequent copying of this section repeats the error or deletes it, or doubles andmutates into a new fragment.
Another reason for frequent spontaneous mutations is a large number of pseudogenes. Because of this, unequal homologous recombinations can form during meiosis. This results in rearrangements in genes, turns and doublings of individual nucleotide sequences.
Polymerase model of mutagenesis
According to this model, spontaneous mutations occur as a result of random errors in the molecules that synthesize DNA. For the first time, such a model was presented by Bresler. He suggested that mutations appear due to the fact that polymerases in some cases insert non-complementary nucleotides into the sequence.
Years later, after lengthy tests and experiments, this point of view was approved and accepted in the scientific world. Certain patterns have even been deduced that allow scientists to control and direct mutations by exposing certain sections of DNA to ultraviolet light. So, for example, it was found that adenine is most often embedded opposite the damaged triplet.
Tautomeric model of mutagenesis
Another theory explaining spontaneous and artificial mutations was proposed by Watson and Crick (the discoverers of the structure of DNA). They suggested that mutagenesis is based on the ability of some DNA bases to turn into tautomeric forms that change the way the bases are connected.
After publication, the hypothesis was actively developed. New forms of nucleotides were discovered afterirradiating them with ultraviolet light. This gave scientists new opportunities for research. Modern science is still debating the role of tautomeric forms in spontaneous mutagenesis and its influence on the number of detected mutations.
Other models
Spontaneous mutation is possible in violation of the recognition of nucleic acids by DNA polymerases. Poltaev and co-authors elucidated the mechanism that ensures compliance with the principle of complementarity in the synthesis of daughter DNA molecules. This model made it possible to study the regularities of the appearance of spontaneous mutagenesis. Scientists explained their discovery by the fact that the main reason for the change in the structure of DNA is the synthesis of non-canonical pairs of nucleotides.
They suggested that base substitution occurs due to deamination of DNA segments. This leads to a change in cytosine to thymine or uracil. Due to such mutations, pairs of incompatible nucleotides are formed. Therefore, during the next replication, a transition occurs (point replacement of nucleotide bases).
Classification of mutations: spontaneous
There are different classifications of mutations depending on what criterion they are based on. There is a division according to the nature of the change in the function of the gene:
- hypomorphic (mutated alleles synthesize fewer proteins, but they are similar to the original ones);
- amorphous (the gene has completely lost its functions);
- antimorphic (the mutated gene completely changes that trait, which represents);- neomorphic (new signs appear).
But a more common classification that divides all mutations in proportion to the variablestructure. Highlight:
1. Genomic mutations. These include polyploidy, that is, the formation of a genome with a triple or more set of chromosomes, and aneuploidy, the number of chromosomes in the genome is not a multiple of the haploid number.
2. Chromosomal mutations. Significant rearrangements of individual sections of chromosomes are observed. There is a loss of information (deletion), its doubling (duplication), a change in the direction of nucleotide sequences (inversion), as well as the transfer of chromosome sections to another place (translocation).3. Gene mutation. The most common mutation. In the DNA chain, several random nitrogenous bases are replaced.
Consequences of mutations
Spontaneous mutations are the causes of tumors, storage diseases, dysfunctions of human and animal organs and tissues. If a mutated cell is located in a large multicellular organism, then with a high degree of probability it will be destroyed by triggering apoptosis (programmed cell death). The body controls the process of preserving the genetic material and, with the help of the immune system, gets rid of all possible damaged cells.
In one case out of hundreds of thousands, T-lymphocytes do not have time to recognize the affected structure, and it gives rise to a clone of cells that also contain the mutated gene. The conglomerate of cells already has other functions, produces toxic substances and negatively affects the general condition of the body.
If the mutation occurred not in the somatic, but in the germ cell, then the changes will be observed in the descendants. They areare manifested by congenital organ pathologies, deformities, metabolic disorders and storage diseases.
Spontaneous mutations: meaning
In some cases, previously seemingly useless mutations can be useful for adapting to new living conditions. This represents mutation as a measure of natural selection. Animals, birds and insects are camouflaged according to their area of residence to protect themselves from predators. But if their habitat changes, then with the help of mutations, nature tries to protect the species from extinction. Under new conditions, the fittest survive and pass this ability on to others.
Mutation can occur in inactive regions of the genome, and then no visible changes in the phenotype are observed. It is possible to detect "breakage" only with the help of specific studies. This is necessary to study the origin of related animal species and draw up their genetic maps.
The problem of spontaneity of mutations
In the 40s of the last century, there was a theory that mutations are caused solely by the influence of external factors and help to adapt to them. In order to test this theory, a special test and repetition method was developed.
The procedure consisted in the fact that a small amount of bacteria of the same species was sown on test tubes and after several inoculations antibiotics were added to them. Some of the microorganisms survived and were transferred to a new medium. Comparison of bacteria from different tubes showed that resistance arosespontaneously, both before and after exposure to antibiotics.
The method of repetition was that microorganisms were transferred to a fleecy cloth, and then transferred simultaneously to several clean media. New colonies were cultured and treated with an antibiotic. As a result, bacteria located in the same parts of the medium survived in different test tubes.
