Mutation is a permanent change in the DNA sequence that makes up a gene. Mutation range in size from one DNA base to a whole chromosome change.

Gene mutation can occur in two ways:

  • Germ line Mutation or hereditary Mutation – Mutations that can be passed down (are hereditary) and are present in all cells of an individual, including the germ cells.
  • Acquired or sporadic Mutations – Mutations caused by genetic changes that happen mostly by chance and are not inherited. They are acquired sometime during a person’s lifetime. These genetic changes are called sporadic (spontaneous) or acquired mutations. Most of these mutations occur in somatic cells. Somatic cells are any cells in the body other than egg and sperm cells (germ cells). Mutations in somatic cells cannot be passed down from a parent to a child.

These changes can be caused by environment factors such as ultraviolet radiation from the sun, or can occur due to the errors that occur during cell division. Errors in replication and damage to DNA have two consequences:

  • Permanent change to DNA, which can alter the coding sequence of a gene or its regulatory sequences.
  • Some chemical alterations to the DNA prevents its use as a template for replication and transcription.

The perpetuation of the genetic material from generation to generation depends on the maintaining rates of mutation at low levels. High rates of mutation in the germ line would destroy the species (lead to species extinction), and high rates of mutation in the soma would destroy the individual (leads to development of new species along with the existing one).

Sources of Mutation:

  1. Inaccuracy in DNA replication: The enzymatic machinery for replicating DNA attempts to cope with the mismatch incorporation of incorrect nucleotides through a proofreading mechanism, but some errors escape detection.
  2. Chemical Damage: Natural and unnatural chemicals and radiations break its backbone and chemically alters its bases. Example: UV radiation, X- ray and Gamma Radiation.
  3. Transposons: It is a DNA sequence that can change its position within the genome, sometimes creating or reversing mutations and altering the cell’s genome size. It can insert large portion of base pairs (may be even thousand bp) from one place to another.

Types of Mutation:

Mutation may  be gross or large ( which contain large portion or whole chromosome), or point (mutations not visible as cytological abnormalities), which can involve change in just a single nucleotide pair in DNA.

A. Base Pair (Nucleotide Pair) Substitutions:

Base pair substitution are the simplest mutation and involve switching of one base pair for another. These are of two types:

  • Transitions (Purine to purine or pyrimidine to pyrimidine substitution)
  • Transversions (Purine to pyrimidine or pyrimidine to purine substitution)

The consequences of base substitution mutations in protein coding regions of a gene depends on the substitution and its location. They may be

Silent: not resulting in a new amino acid in the protein sequence, eg GCA or GCG codons in mRNA both mean Arginine.

Missense Mutation: A base substitutaion which result in amino acid substitution. Eg. CTC in the DNA sense strand will specify glumate residue in the protein; this is altered to CAC in the DNA or GUG in the mRNA, resulting in a Valine residue in the beta-globulin protein chain causing sickle-cell anemia.

Nonsense Mutation: Base substitutions in a protein coding region may mutate an amino acid codon to termination code or vise versa, which results in a prematurely shortened protein.

Base substitution mutation may also occur in promoters or 5′ regulatory regions of genes or in introns and may affect their transcription, translation, or splicing. Many of the beta-thalassemias are the result of these types of non-structural mutations that may affect the level of expression of the globin genes. All of the types of the mutation described above have been observed in human globin genes. Their consequences depends on what they do to the level of expression of the gene products and/or on what amino acid substitution may have occured and where it is in the protein.

B. Frameshift Mutation (Insertions, Deletions and Duplications)

These result from insertion or deletion of one or more nucleotides in the coding region of the gene. This causes an alteration of the reading frame: since codons are groups of three nucleotides, there are three possible reading frames for each gene although only one is used. A mutation of this sort changes all the amino acids downstream and is very likely to create a nonfunctional product since it may differ greatly from the normal protein.

C. Repeat Expansions

Nucleotide repeats are short DNA sequences that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of 3-bp sequences. A repeat expansion is a mutation that increase the number of times that the short DNA sequence is repeated. This type of mutation can cause resulting protein to function improperly.

D. Changes in Chromosomes

Changes that affect entire chromosomes or segments of the chromosomes can cause problems with growth, development, and function of the body’s systems. These changes can affect many gene along the chromosome and alter the proteins made by these genes. Conditions caused by the change in the number or structure of chromosomes are known as chromosomal disorders. these changes can occur during the formation of productive cells or in early fetal development. Many cancer cells also have changes in their chromosome number or structure. These changes most often occur in somatic cells during a person’s lifetime.

Proneness to Mutations

DNA sequences contain regions which are more prone to mutation. These mutation-prone sequences are repeats of simple di, tri, or teranucleotide sequences, which are known as DNA microsatellites.


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