Mutations

A mutation is a change in the genetic information in an organism. For example, when a sequence of CGA gets changed into AGA, we talk about a mutation.

There are many ways by which mutations are classified.

The first classification takes into account in which cells mutations occur. Somatic mutations can occur in any type of cell in the body except for germ cells. For that reason, they cannot be passed on to future generations. Germ-line mutations, on the other hand, occur in germ cells and do therefore pass on to future generations.

The second classification distinguishes between gene mutations, which usually affect only one gene, and chromosome mutations, which change the number or the structure of chromosomes.

Another classification considers the mechanism by which a mutation occurs. The simplest gene mutation is a base substitution - a mutation in which one nucleotide is replaced by another one. There are two types of base substitution, a) transition, when a purine is replaced by another purine or a pyrimidine is replaced by another pyrimidine, b) transversion, when a purine is replaced by a pyrimidine or a pyrimidine is replaced by a purine. We also distinguish insertions, mutations in which one or more nucleotides are added, and deletions, mutations in which one or more nucleotides are removed.

Insertions and deletions are dangerous mutations as they can lead to the so-called frameshift mutations. Frameshift mutations are changes in the reading frame of a gene - simply said, these mutations change the way a gene is read. As you can see in the example below, a deletion of one base will cause a frameshift mutation and different amino acids (Leu, Gly) are going to be synthesized. The mutation can also change a sense codon (a codon that specifies an amino acid) into a stop codon and stop the protein synthesis altogether.

There are also forward and reverse mutations. A forward mutation is a mutation that results in an altered phenotype (phenotype = observable characteristics of an organism). A reverse mutation then reverts this altered phenotype into the original one. For example, a forward mutation could change the colour of the eyes from green to brown. A reverse mutation would then revert the change from brown to green. Of course, in reality, this is much more complicated and this example is only hypothetical.

Another classification considers the effect the mutation has on the structure of a protein. A missense mutation is a base substitution that changes the codon in a way that a different amino acid is synthesized. A nonsense mutation changes a codon that specifies an amino acid into a stop codon. A silent mutation changes a codon that specifies a certain amino acid into a different codon that however specifies the same amino acid.

A special type of mutation is the suppressor mutation, which suppresses the effect of another mutation. There are two types of the suppressor mutation: 1) intragenic, 2) intergenic (extragenic). The intragenic suppressor mutation occurs in the gene where the mutation it suppresses is located. The intergenic (extragenic) suppressor mutation, on the other hand, occurs in a different gene than the one where the mutation it suppresses is located.

Another interesting type of mutation are the expanding nucleotide repeats. These mutations increase the number of copies of a set of nucleotides (usually three). These mutations cause, for example, the fragile X syndrome in which the number of copies of the CGG set of nucleotides located on the X chromosome increases up to 1500 copies. Expanding nucleotide repeats are also the cause of Huntington disease, Kennedy disease and many others.

What causes mutations?

Mutations that occur randomly, for example by an error in DNA replication, are called spontaneous mutations. They can involve spontaneous chemical changes in DNA, such as depurination (the removal of a purine base from a nucleotide), depyrimidination (the removal of a pyrimidine base from a nucleotide), or deamination (the removal of an amino acid group from cytosine (usually) producing uracil).

However, mutations can also be caused by chemical, biological or physical agents in the environment. These are called induced mutations. Some chemicals can induce deamination, which we mentioned earlier. Chemicals called base analogs have structures similar to the standard bases in DNA and as a result can be incorporated into newly synthesized DNA molecules during replication. Chemicals called alkylating agents donate alkyl groups (e.g., methyl (CH3-)) to nucleotide bases inducing all types of mutations. Chemicals referred to as intercalating agents (e.g., ethidium bromide) place themselves (intercalate) between adjacent bases in DNA damaging the helix structure and causing insertions and deletions in replication that often result in severe frameshift mutations. UV light can be quite damaging as it is absorbed by pyrimidine bases and it causes the formation of chemical bonds between adjacent pyrimidine molecules creating pyrimidine dimers (usually thymine) that often block replication.

Finally, we should mention that the frequency of new mutations occurring in a gene or in the organism is called the mutation rate. Any agent in the environment that causes mutations is called a mutagen.

References:
Pierce, B. A. (2019). Genetics: A Conceptual Approach (Seventh ed.). W. H. Freeman.
Snustad, D. P., & Simmons, M. J. (2012). Principles of Genetics. Wiley