What mutations are called spontaneous? If you translate the term into an accessible language, then these are natural errors that occur during the interaction of genetic material with the internal and / or external environment. Such mutations are usually random. They are observed in the reproductive and other cells of the body.
Exogenous causes of mutations
Spontaneous mutation can occur under the influence of chemicals, radiation, under the influence of high or low temperatures, rarefied air or high pressure.
Each year, an average person absorbs about one tenth of a radion of ionizing radiation, which makes up the natural background radiation. This number includes gamma radiation from the Earth’s core, the solar wind, the radioactivity of elements lying in 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 precisely because of this factor.
Ultraviolet radiation, contrary to popular belief, plays an insignificant role in the 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, unicellular 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 due to which a spontaneous mutation can occur are endogenous factors. These include by-products of metabolism, errors in the process of replication, repair or recombination, and others.
- Replication Failures:
- spontaneous transitions and inversions of nitrogen bases;
- incorrect insertion of nucleotides due to DNA polymerase errors;
- chemical replacement of nucleotides, for example, guanine-cytosine with adenine-guanine. - Recovery 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 crossing-over processes during meiosis or mitosis lead to loss and completion of the bases.
These are the main factors causing spontaneous mutations. The causes of 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 still structural factors. These include repetitions of the nucleotide sequence close to the place of chain rearrangement, the presence of additional DNA sections similar in structure to the gene, as well as the mobile elements of the genome.
Mutagen pathogenesis
Spontaneous mutation occurs due to the influence of all of the above factors, acting together or separately in a certain period of cell life. There is such a phenomenon as a sliding violation of the mating of the daughter and maternal DNA strands. As a result of this, loops of peptides are often formed that could not adequately integrate into the sequence. After removing the extra DNA sections from the daughter chain, loops can be either resected (deletions) or embedded (duplications, insertions). The appeared changes are fixed in the following cycles of cell division.
The speed and number of mutations that occur depends on the primary structure of DNA. Some scientists believe that absolutely all DNA sequences are mutagenic if they form bends.
The most common spontaneous mutations
What are the most common manifestations of spontaneous mutations in genetic material? Examples of such conditions are loss of nitrogenous bases and removal of amino acids. Especially sensitive to them are cytosine residues.
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 and mutates 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. The consequence of this are rearrangements in genes, rotations and doubling of individual nucleotide sequences.
Polymerase mutagenesis model
According to this model, spontaneous mutations result from random errors in DNA synthesizing molecules. For the first time, a similar model was introduced by Bresler. He suggested that mutations appear due to the fact that polymerases in some cases integrate 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 radiation. So, for example, we found out that opposite to the damaged triplet adenine is most often embedded.
Tautomeric mutagenesis model
Another theory explaining spontaneous and artificial mutations was proposed by Watson and Crick (the discoverers of DNA structure). They suggested that mutagenesis is based on the ability of certain DNA bases to transform into tautomeric forms that change the way the bases are joined.
After publication, the hypothesis was actively developed. New forms of nucleotides were discovered after irradiation with ultraviolet light. This gave scientists new opportunities for research. Modern science still debates the role of tautomeric forms in spontaneous mutagenesis and its effect on the number of detected mutations.
Other models
Spontaneous mutation is possible with impaired recognition of nucleic acids by DNA polymerases. Poltaev et al. Clarified a mechanism that ensures compliance with the principle of complementarity in the synthesis of daughter DNA molecules. This model allowed us to study the patterns of spontaneous mutagenesis. Scientists explained their discovery by the fact that the main reason for changing the structure of DNA is the synthesis of non-canonical nucleotide pairs.
They suggested that base sweeping occurs due to deamination of DNA sites. 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 substitution of nucleotide bases).
Mutation Classification: Spontaneous
There are different classifications of mutations, depending on which criterion lies in their basis. There is a separation according to the nature of changes in gene function:
- hypomorphic (mutated alleles synthesize fewer proteins, but they are similar to the original ones);
- amorphous (the gene has completely lost its functions);
- antimorphic (a mutated gene completely changes the trait that it represents);
- neomorphic (new signs appear).
But a more common classification is that divides all mutations in proportion to a variable structure. Allocate:
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 one.
2. Chromosomal mutations. Significant rearrangements of individual chromosome regions are observed. There are information loss (deletion), its doubling (duplication), change in the direction of nucleotide sequences (inversion), as well as transfer of chromosome sites to another place (translocation).
3. Gene mutation. The most common mutation. In the DNA chain, several random nitrogen bases are replaced.
Effects of mutations
Spontaneous mutations are the causes of tumors, diseases of accumulation, dysfunctions of organs and tissues of humans and animals. If the mutated cell is located in a large multicellular organism, then it will most likely 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 a clone of cells that also contain a mutated gene. A conglomerate of cells already has other functions, it produces toxic substances and negatively affects the general condition of the body.
If the mutation occurred not in the somatic, but in the reproductive cell, then the changes will be observed in the descendants. They are manifested by congenital pathologies of organs, malformations, metabolic disorders and diseases of accumulation.
Spontaneous mutations: meaning
In some cases, mutations that previously seemed useless may be useful to adapt to new living conditions. This represents the mutation as a measure of natural selection. Animals, birds, and insects are camouflaged to the 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 the new conditions, the fittest survive and pass on this ability to others.
Mutation can occur in inactive parts of the genome, and then no visible phenotype changes are observed. It is possible to detect a “breakdown” only with the help of specific studies. This is necessary to study the origin of related animal species and compile their genetic maps.
The problem of spontaneity of mutations
In the forties of the last century, there was a theory that mutations are caused solely by external factors and help them adapt. In order to test this theory, a special test and repetition method was developed.
The procedure was that a small number of bacteria of the same species were plated on test tubes and antibiotics were added to them after several inoculations. Some microorganisms survived, and they were transferred to a new environment. A comparison of bacteria from different test tubes showed that resistance arose spontaneously, both before and after contact with the antibiotic.
The method of repetition was that microorganisms were transferred to the fleecy tissue, and then transferred simultaneously to several clean media. New colonies were cultured and treated with antibiotic. As a result, bacteria located in identical parts of the medium survived in different test tubes.