Spontaneous mutation: classification, causes, examples

What mutations are called spontaneous? If you translate the term into an accessible language, then these are natural errors that arise during the interaction of genetic material with the internal and / or external environment. Such mutations are usually random. They are observed in the genital and in 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.

Every year, on average, a person absorbs about one tenth of a series of ionizing radiation, which is a natural radiation background. This number includes the gamma radiation of the Earth's core, the solar wind, the radioactivity of elements lying in the thickness of the earth's crust and dissolved in the atmosphere. The dose obtained depends also 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 a minor role in the occurrence of DNA breakdowns, since it can not penetrate deep enough into the human body. But the skin often suffers from excessive insolation (melanoma and other cancers). However, unicellular organisms and viruses mutate under the influence of sunlight.

Too high or low temperatures can also cause changes in the genetic material.

Endogenous causes of mutations

The main reasons for which a spontaneous mutation may occur are endogenous factors. These include by-products of metabolism, errors in the process of replication, repair or recombination, and others.

1. Replication failures:
   - spontaneous transitions and inversions of nitrogenous bases;
   - incorrect incorporation of nucleotides due to DNA polymerase errors;
   - chemical replacement of nucleotides, for example, guanine-cytosine by adenine-guanine.
2. Recovery errors:
   - mutations in the genes responsible for repairing individual parts of the DNA chain after their rupture under the influence of external factors.
3. Problems with recombination:
   - failures in the processes of crossing-over under meiosis or mitosis lead to the deposition and completion of the bases.

These are the main factors causing spontaneous mutations. The causes of malfunctions can be the activation of mutator genes, as well as the transformation of safe chemical compounds into more active metabolites that affect the nucleus of the cell. In addition, there are still structural factors. These include repeating the sequence of nucleotides near the site of the chain rearrangement, the presence of additional DNA sections similar in structure to the gene, as well as the mobile elements of the genome.

Pathogenesis of mutation

Spontaneous mutation arises from the impact 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 disruption of the mating of the daughter and maternal DNA strands. As a result, loops of peptides are often formed, which could not be adequately incorporated into the sequence. After removing excess DNA from the daughter chain, loops can both be resected (deletions) and embedded (duplications, insertions). The changes are fixed in the next cycles of cell division.

The rate and number of mutations that arise depend on the primary DNA structure. Some scientists believe that absolutely all DNA sequences have mutagenicity, if they form bends.

The most common spontaneous mutations

What is most often manifested in the genetic material of spontaneous mutations? Examples of such states are the loss of nitrogenous bases and the removal of amino acids. Cytosine residues are particularly susceptible to them.

It is proved that to date, 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 it and mutates it into a new fragment.

Another reason for the frequent spontaneous mutations is a large number of pseudogenes. Because of this, in the process of meiosis, unequal homologous recombinations can form. A consequence of this are the rearrangements in the genes, rotations and doubling of the individual nucleotide sequences.

Polymerase model of mutagenesis

According to this model, spontaneous mutations arise as a result of random errors of molecules synthesizing DNA. For the first time such a model was presented by Bresler. He suggested that mutations are due to the fact that polymerases in some cases incorporate uncomplimentary nucleotides into the sequence.

Years later, after lengthy inspections and experiments, this view was approved and accepted in the scientific world. Some regularities have been derived that allow scientists to control and direct mutations by exposing certain regions of DNA to ultraviolet radiation. For example, it was found that adrenine is most often built in front of a damaged triplet.

Tautomeric model of mutagenesis

Another theory that explains spontaneous and artificial mutations was suggested by Watson and Crick (the discoverers of the DNA structure). They suggested that mutagenesis is based on the ability of certain DNA bases to transform into tautomeric forms that alter the way in which the bases are joined.

After publication, the hypothesis was actively developed. New forms of nucleotides were discovered after irradiation with their ultraviolet. This gave scientists new opportunities for research. Modern science is still debating the role of tautomeric forms in spontaneous mutagenesis and its effect on the number of mutations detected.

Other models

Spontaneous mutation is possible if DNA DNA polymerases are not recognized by nucleic acids. Poltayev and co-authors clarified the mechanism that ensures the principle of complementarity in the synthesis of daughter DNA molecules. This model allowed to study the regularities of the appearance of spontaneous mutagenesis. Scientists explained their discovery by the fact that the main cause of the change in the structure of DNA is the synthesis of non-canonical pairs of nucleotides.

They suggested that the swelling of the bases is due to deamination of DNA sections. This leads to a change in cytosine to thymine or uracil. Because of such mutations, pairs of incompatible nucleotides are formed. Therefore, during the next replication, there is a transition (point substitution of nucleotide bases).

Classification of mutations: spontaneous

There are different classifications of mutations depending on which criterion is at their basis. There is a separation 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);
- antimorphous (mutated gene completely changes the sign that it represents);
- neomorphic (new signs appear).

But the classification is more common, which divides all mutations in proportion to the mutable structure. Allocate:

1. Genomic mutations. These include polyploidy, that is, the formation of a genome with a triple or more chromosome set, and aneuploidy - the number of chromosomes in the genome is not a multiple of the haploid.
2. Chromosome mutations. There are significant changes in some parts of the chromosomes. Distinguish between the loss of information (deletion), its duplication (duplication), the change in the direction of nucleotide sequences (inversion), and the transfer of chromosome regions 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, accumulation diseases, dysfunctions of organs and tissues of humans and animals. If the 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 genetic material and by means 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. The conglomerate of cells has already other functions, it produces toxic substances and negatively affects the general state of the body.

If the mutation occurred not in the somatic but in the sex cell, then the changes will be observed in the offspring. They are manifested by congenital pathologies of organs, deformities, metabolic disorders and accumulation diseases.

Spontaneous mutations: significance

In some cases, previously mutually useless mutations may be useful for adaptation in new conditions of life. This represents the mutation as a measure of natural selection. Animals, birds and insects have a camouflage coloration, corresponding to the area of residence, to protect themselves from predators. But if their habitat varies, then with the help of mutations nature tries to protect the species from extinction. In the new conditions, the fittest survive and transfer this ability to others.

Mutation can occur in inactive parts of the genome, and then no visible changes in the phenotype are observed. To detect a "breakdown" is possible only with the help of specific studies. This is necessary for studying the origin of related animal species and drawing up 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 the influence of external factors and help them adapt. In order to test this theory, a special test and a method of repetition was developed.

The procedure consisted in the fact that a small number of bacteria of one species were sown on test tubes and after several inoculations antibiotics were added to them. Some of the microorganisms survived, and they were transferred to a new environment. Comparison of bacteria from different test tubes showed that resistance appeared spontaneously, both before and after antibiotic contact.

The method of repetition was that microorganisms were transferred to the fleecy tissue, and then transferred to several pure media simultaneously. The new colonies were cultured and treated with an antibiotic. As a result, bacteria in different test tubes survived on the same parts of the medium.