Genomic Mutations: Classification, Causes, Consequences and Laboratory Methods to Generate Mutations

Nowadays, most scientists consider the term “mutation” to describe a change in an individual gene.

More precisely as a tiny alteration of the DNA of that gene, especially a substitution of nucleotides.

But the idea of ​​mutation has changed considerably concerning the mendelian concepts of Darwin’s generation, which saw “fluctuating variations” as the raw material on which evolution operated, up to the current genomic context of today’s mutation in the day.

A genetic mutation is a permanent alteration in the DNA sequence that makes up a gene, so the sequence differs from what is found in most people.

Mutations vary in size; they can affect a single DNA building block (base pair) to a large segment of a chromosome that includes multiple genes.

There are many types of mutations; for example, a point mutation occurs when a single nucleotide is replaced by another single nucleotide.

An insertion mutation occurs when a different portion of DNA is added to a chromosomal region.


On the other hand, a mutation by deletion occurs when a part of the DNA sequence is missing in the genome.

Classification of mutations

Mutations can be classified as follows:

Hereditary mutations

These are inherited from a father and are present throughout the patient’s life in almost all cells of the body.

These mutations are also called germline mutations because they are present in the ovum or sperm cells of the parent, which are also called germ cells.

When an egg and a sperm come together, the resulting fertilized egg receives DNA from both parents.

If this DNA has a mutation, the child that grows from the fertilized egg will have the mutation in each of its cells.

Mutations acquired (or somatic)

These occur at some point during a person’s life and are present only in specific cells, not in every body cell.

They can be caused by some environmental factors, such as the effect of ultraviolet radiation or as a result of an error when DNA copies itself in cell division.

Mutations acquired in somatic cells (cells other than sperm and ovules) can not be passed on to the next generation.

The genetic changes described as de novo (new) mutations can be hereditary or somatic.

In some cases, the mutation occurs in a person’s egg or sperm but is not present in any of the other cells of the person.

In other cases, the mutation occurs in the fertilized egg shortly after the egg and the sperm cells come together (it is often impossible to say precisely when a de novo mutation occurred).

As the fertilized egg divides, each cell resulting in the growing embryo, will have the mutation.

De novo mutations can explain the genetic disorders in which an affected child has a mutation in every body cell. Still, the parents do not, and there is no family history of the disease.

Somatic mutations that occur in a single cell at the start of embryonic development can lead to mosaicism.

These genetic changes are not present in the ovum or sperm cells of a parent or the fertilized egg but occur a little later in the embryo and include several cells.

As all cells divide during growth and development, the cells that arise from the cell with the altered gene will have the mutation, while others will not.

Depending on the mutation and the number of affected cells, mosaicism may not cause health problems.

Most genetic mutations that cause disease are rare in the general population. However, other genetic changes occur more frequently.

Consequences of mutations

The consequence of having a mutation in the genome also varies.

A mutation cannot affect an organism if the transformation occurs in a region that does not affect the gene products or the functions of the genes.

This can happen if the mutation occurs in the non-coding region of the DNA or if the mutation occurs in a coding region but does not change the final amino acid sequence of the gene product. This type of genetic alteration is called a silent mutation.

The silent mutation is the primary type of mutation in our genome.

Suppose a mutation changes the amino acid sequence of a gene product or alters its expression. In that case, phenotypic consequences can occur, which could affect the level of fitness of the organism in its environment.

A mutation is advantageous when its phenotypic consequence allows the organism to be more adaptable to the environment.

On the contrary, a mutation is harmful when the organism becomes less adaptable to its environment.


Mutations can accumulate naturally in two ways.

It can be transmitted from parents to children, which is called a hereditary mutation or acquired throughout the life of an organism.

These acquired mutations occur intrinsically from errors during DNA replication in actively dividing cells.

They can also be induced extrinsically by external factors, such as UV radiation and free radicals.

Organisms acquire mutations through intrinsic and extrinsic factors with regularity, which causes variations in our genome.

The variation caused by the mutation of the genome is essential for the long-term survival of the species since it provides the basis for natural selection, evolution, and adaptation to the changing environment over time.

Laboratory methods to generate mutations

Mutations can also be intentionally introduced into a laboratory environment.

Over the years, scientists have developed techniques to generate genetic mutations in model organisms.

These techniques are powerful tools for scientists to study the functions of genes and proteins.

Random mutagenesis

Random mutagenesis is a method that unexpectedly generates mutations.

Random mutagenesis can be achieved by using external mutagens, such as radiation or mutagenic chemicals.

It can also be achieved by using error-prone DNA polymerases that introduce incorrect nucleotides during DNA replication.

Random mutagenesis was one of the first tools available to introduce mutations in the genome. It has continued to be used to generate random sequences of genes and proteins.

Site-directed mutagenesis

Site-directed mutagenesis is a method that generates specific nucleotide changes at a desired location in the genome.

The technique is achieved by polymerase chain reactions using primers containing desired mutations.

The mutant plasmid can then be obtained through sequential purification steps by polymerase chain reactions, template degradation, E. coli transformation, and plasmid isolation.

Site-directed mutagenesis is a powerful technique for introducing mutations.

As long as the primers can hybridize to the desired locus, more than one mutation can be introduced into the primers.

Therefore, mutations generated by site-directed mutagenesis can be single-point mutations, multiple point mutations, insertions, or deletions.

Therefore, site-directed mutagenesis is a versatile tool for introducing a wide range of mutations in the genome.

Blocking genes and genes driven by homologous recombination

Homologous recombination is a natural process that facilitates the exchange of genetic materials between two similar DNA sequences.

It is involved in repairing DNA damage, such as breaks in the double strand of DNA.

It also promotes the exchange of genetic materials between homologous chromosomes in meiosis for spores and the production of gametes.

Throughout evolution, the conservation of human genomes has allowed scientists to perform high-precision gene inactivation and gene selection in many model organisms, such as bacteria, yeast, and mice.

A host gene is replaced with a selectable marker in a typical gene selection scenario.

The selectable marker is amplified by polymerase chain reactions so that the flanking sequences are identical to the ascending and descending lines of the host gene.

The flanking sequences are necessary for homologous recombination to guide and integrate the marker into the host genome at the desired locus.

Mutation collections by elimination

With the help of high-precision robotics, elimination collections have allowed scientists to perform high-throughput screening assays to detect pharmacological targets, identify genetic interactions at the genomic level, and study the complexity of genetic networks.