Mutagenic Agents: How They Act, Types And Examples

The mutagenic agents, also known mutagens, are molecules of a different nature that cause changes in the bases that form part of the DNA strands. In this way, the presence of these agents amplifies the rate of mutation in the genetic material. They are classified into physical, chemical and biological mutagens.

Mutagenesis is a ubiquitous event in biological entities, and does not necessarily translate into negative changes. In fact, it is the source of variation that enables evolutionary change.

DNA can be damaged by UV light.

Source: derivative work: Mouagip (talk) DNA_UV_mutation.gif: NASA / David HerringThis W3C-unspecified vector image was created with Adobe Illustrator. [Public domain]

Article index

  • one

    What is a mutation?

    • 1.1

      Are mutations always lethal?

    • 1.2

      How do mutations arise?

  • two

    Types of mutagenic agents

    • 2.1

      Chemical mutagens

    • 2.2

      Physical mutagens

    • 23

      Biological mutagens

  • 3

    How do they work ?: types of mutations caused by mutagenic agents

    • 3.1

      Base tautomerization

    • 3.2

      Incorporation of analogous bases

    • 3.3

      Direct action on the bases

    • 3.4

      Adding or deleting bases

  • 4

    References

What is a mutation?

Before going into the subject of mutagens, it is necessary to explain what a mutation is. In genetics, a mutation is a permanent and heritable change in the sequence of nucleotides in the molecule of genetic material: DNA.

All the information necessary for the development and control of an organism resides in its genes – which are physically located on the chromosomes. Chromosomes are made up of one long molecule of DNA.

Mutations generally affect the function of a gene and it can lose or modify its function.

Since a change in the DNA sequence affects all copies of proteins, certain mutations can be extremely toxic to the cell or to the body in general.

Mutations can occur at different scales in organisms. Point mutations affect a single base in DNA, while larger-scale mutations can affect entire regions of a chromosome.

Are mutations always lethal?

It is incorrect to think that the mutation always leads to the generation of diseases or pathological conditions for the organism that carries it. In fact, there are mutations that do not change the sequence of proteins. If the reader wants to better understand the reason for this fact, he can read about the degeneracy of the genetic code.

In fact, in the light of biological evolution, the sine qua non condition for change to occur in populations is the existence of variation. This variation arises by two main mechanisms: mutation and recombination.

Thus, in the context of Darwinian evolution, it is necessary for there to be variants in the population – and for these variants to be associated with greater biological adequacy.

How do mutations arise?

Mutations can arise spontaneously or they can be induced. The intrinsic chemical instability of nitrogenous bases can result in mutations, but at a very low frequency.

A common cause of spontaneous point mutations is cytosine deamination to uracil in the DNA double helix. The replication process of this strand leads to a mutant daughter, where the original GC pair has been replaced by an AT pair.

Although DNA replication is an event that occurs with surprising precision, it is not entirely perfect. Errors in DNA replication also lead to spontaneous mutations.

Furthermore, the natural exposure of an organism to certain environmental factors leads to the appearance of mutations. Among these factors we have ultraviolet radiation, ionizing radiation, various chemicals, among others.

These factors are mutagens. We will now describe the classification of these agents, how they act and their consequences in the cell.

Types of mutagenic agents

The agents that cause mutations in genetic material are very diverse in nature. First, we will explore the classification of mutagens and give examples of each type, then we will explain the different ways that mutagens can cause changes in the DNA molecule.

Chemical mutagens

Mutagens of a chemical nature include the following classes of chemicals: acridines, nitrosamines, epoxides, among others. There is a sub-classification for these agents in:

Analogous bases

Molecules that show structural similarity to nitrogenous bases have the ability to induce mutations; among the most common are l 5-bromouracil and 2-aminopurine.

Agents that react with genetic material

Nitrous acid, hydroxylamine, and a number of alkylating agents react directly on the bases that make up DNA and can change from purine to pyrimidine and vice versa.

Interheating agents

There are a series of molecules such as acridines, ethidium bromide (widely used in molecular biology laboratories) and proflavin, which have a flat molecular structure and manage to enter the DNA strand.

Oxidative reactions

The normal metabolism of the cell has as a secondary product a series of reactive oxygen species that damage cellular structures and also genetic material.

Physical mutagens

The second type of mutagenic agents are physical. In this category we find the different types of radiation that affect DNA.

Biological mutagens

Lastly, we have the biological mutants. They are organisms that can induce mutations (including abnormalities at the chromosome level) in viruses and other microorganisms.

How do they work ?: types of mutations caused by mutagenic agents

The presence of mutagenic agents cause changes in the bases of DNA. If the result involves the change of a puric or pyrimidine base for one of the same chemical nature, we speak of a transition.

In contrast, if the change occurs between bases of different types (a purine for a pyrimidine or the opposite) we call the process a transversion. Transitions can occur for the following events:

Base tautomerization

In chemistry, the term isomer is used to describe the property of molecules with the same molecular formula to have different chemical structures. Tautomers are isomers that only differ from their peers in the position of a functional group, and there is a chemical equilibrium between the two forms.

One type of tautomerism is keto-enol, where the migration of a hydrogen occurs and alternates between both forms. There are also changes between the imino to amino form. Thanks to its chemical composition, the bases of DNA experience this phenomenon.

For example, adenine is normally found as amino and pairs – normally – with thymine. However, when it is in its imino isomer (very rare) it pairs with the wrong base: cytosine.

Incorporation of analogous bases

Incorporating base-like molecules can disrupt the base-pairing pattern. For example, the incorporation of 5-bromouracil (instead of thymine) behaves like cytosine and leads to the replacement of an AT pair by a CG pair.

Direct action on the bases

The direct action of certain mutagens can directly affect the bases of DNA. For example, nitrous acid converts adenine to a similar molecule, hypoxanthine, through an oxidative deamination reaction. This new molecule pairs with cytosine (and not thymine, as adenine normally would).

The change can also occur on cytosine, and uracil is obtained as a product of deamination. Single base substitution in DNA has direct consequences on the transcription and translation processes of the peptide sequence.

A stop codon may appear early, and translation stops prematurely, affecting the protein.

Adding or deleting bases

Some mutagens such as intercalating agents (acridine, among others) and ultraviolet radiation have the ability to modify the nucleotide chain.

By intercalating agents

As we mentioned, interheating agents are flat molecules, and they have the ability to intercalate (hence their name) between the bases of the strand, distorting it.

At the time of replication, this deformation in the molecule leads to the deletion (that is, to a loss) or insertion of bases. When DNA loses bases or new ones are added, the open reading frame is affected.

Remember that the genetic code involves the reading of three nucleotides that code for an amino acid. If we add or remove nucleotides (in a number that is not 3) all the DNA reading will be affected, and the protein will be totally different.

This type of mutation is called frame shift or changes in the composition of triplets.

Ultraviolet radiation

Ultraviolet radiation is a mutagenic agent, and it is a normal non-ionizing component of ordinary sunlight. However, the component with the highest mutagenic rate is trapped by the ozone layer of the Earth’s atmosphere.

The DNA molecule absorbs radiation and the formation of pyrimidine dimers occurs. That is, the pyrimidine bases are linked by means of covalent bonds.

Adjacent thymines on the DNA strand can join to form thymine dimers. These structures also affect the replication process.

In some organisms, such as bacteria, these dimers can be repaired thanks to the presence of a repairing enzyme called photolyase. This enzyme uses visible light to reconvert dimers into two separate bases.

However, nucleotide excision repair is not restricted to errors caused by light. The repair mechanism is extensive, and can repair damage caused by various factors.

When humans overexpose us to the sun, our cells receive excessive amounts of ultraviolet radiation. The consequence is the generation of thymine dimers and they can cause skin cancer.

References

  1. Alberts, B., Bray, D., Hopkin, K., Johnson, AD, Lewis, J., Raff, M.,… & Walter, P. (2015).  Essential cell biology . Garland Science.
  2. Cooper, GM, & Hausman, RE (2000). The cell: Molecular approach . Sinauer Associates.
  3. Curtis, H., & Barnes, NS (1994). Invitation to biology . Macmillan.
  4. Karp, G. (2009). Cell and molecular biology: concepts and experiments . John Wiley & Sons.
  5. Lodish, H., Berk, A., Darnell, JE, Kaiser, CA, Krieger, M., Scott, MP,… & Matsudaira, P. (2008).  Molecular cell biology . Macmillan.
  6. Singer, B., & Kusmierek, JT (1982). Chemical mutagenesis.  Annual review of biochemistry51 (1), 655-691.
  7. Voet, D., & Voet, JG (2006). Biochemistry . Panamerican Medical Ed.

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