Cell and Molecular

Biology
Submitted to:
Prof. Amna
Qammar
Submitted by:
Sidra Shahzadi
(0019)
Class:
BS (Zoology)
Semester:
 5th

Mutation:
Mutation, an alteration in the genetic material (the genome) of a cell of a
living organism or of a virus that is more or less permanent and that can
be transmitted to the cell’s or the virus’s descendants. (The genomes of
organisms are all composed of DNA, whereas viral genomes can be of
DNA or RNA; see heredity: The physical basis of heredity.) Mutation in
the DNA of a body cell of a multicellular organism (somatic mutation)
may be transmitted to descendant cells by DNA replication and hence
result in a sector or patch of cells having abnormal function, an example
being cancer.

Types of Mutation:
Mutations can be classified in various ways depending on the cause of
the mutation, its effect on the function of the gene product or the kind of
changes to the structure of the gene itself.

1-Substitution Mutations:
Substitution mutations are situations where a single nucleotide is
changed into another. In organisms having double-stranded DNA or
RNA, this usually means that the corresponding base pair is also altered.
For example, an A: T base pair could be mutated into a G: C base pair or
even a T:A base pair. Depending on the position of this change, it could
have a variety of effects.
Lastly, the most drastic substitution mutation is one that results in the
premature termination of amino acid elongation because of the sudden
appearance of a stop codon in the middle of the coding sequence. For
instance, if the UAC codon coding for threonine is mutated into a UAA
codon, especially in the 5’ end of the coding sequence, it will likely lead
to an extremely short, possibly non-functional protein.

EXAMPLE:
Sickle cell anemia is caused by a substitution in the beta-
hemoglobin gene, which alters a single amino acid in the protein
produced. Change a codon to one that encodes the same amino
acid and causes no change in the protein produced. These are
called silent mutations.
2-Missense mutation
This type of mutation is a change in one DNA base pair that
results in the substitution of one amino acid for another in the
protein made by a gene.
EXAMPLE:
Missense mutations in the SHP-2 gene have been identified as
the underlying cause of Noonan syndrome. Most of the altered
amino acid residues are located in or around the interacting
surfaces of the N-terminal SH2 domain and the catalytic
domain, and are predicted to relieve the intramolecular
inhibition caused by binding of the SH2 domain to the catalytic
domain.
3-Nonsense mutation
A nonsense mutation is also a change in one DNA base pair. Instead of
substituting one amino acid for another, however, the altered DNA
sequence prematurely signals the cell to stop building a protein. This
type of mutation results in a shortened protein that may function
improperly or not at all.
EXAMPLE:
Diseases in which point-nonsense mutations are known to be among
the causes include: Cystic fibrosis (caused by the G542X mutation in
the [[cystic fibrosis transmembrane conductance regulatory. Beta
thalassemia (β-globin) Hurler syndrome.

4-Insertion:
Insertions add one or more extra nucleotides into the DNA. They are
usually caused by transposable elements, or errors during replication of
repeating elements. Insertions in the coding region of a gene may alter
splicing of the mRNA (splice site mutation), or cause a shift in the
reading frame (frameshift), both of which can significantly alter the gene
product. Insertions can be reversed by excision of the transposable
element.
EXAMPLE:
Beta hemoglobin (beta globin) is a single chain of 147 amino
acids. As previously mentioned, in sickle-cell anemia, the gene for
beta globin is mutated. The resulting protein still consists of 147
amino acids, but because of the single-base mutation, the sixth
amino acid in the chain is valine, rather than glutamic acid.

5-Deletion
Deletions or Deficiency remove one or more nucleotides from the DNA.
Like insertions, these mutations can alter the reading frame of the gene.
In general, they are irreversible: Though exactly the same sequence
might, in theory, be restored by an insertion, transposable elements able
to revert a very short deletion (say 1–2 bases) in any location either are
highly unlikely to exist or do not exist at all.
EXAMPLE:
Diseases that can be caused by deletion mutation can include 22q11. 2
deletion syndrome, cystic fibrosis, Turner syndrome, and Williams’s
syndrome.

6-Frameshift Mutation:
A frameshift mutation is a genetic mutation caused by a deletion or
insertion in a DNA sequence that shifts the way the sequence is read. A
DNA sequence is a chain of many smaller molecules called nucleotides.
DNA (or RNA) nucleotide sequences are read three nucleotides at a time
in units called codons, and each codon corresponds to a specific amino
acid or stop signal. During translation, the sequence of codons is read in
order from the nucleotide sequence to synthesize a chain of amino acids
and form a protein. Frameshift mutations arise when the normal
sequence of codons is disrupted by the insertion or deletion of one or
more nucleotides, provided that the number of nucleotides added or
removed is not a multiple of three. For instance, if just one nucleotide is
deleted from the sequence, then all of the codons including and after the
mutation will have a disrupted reading frame. This can result in the
incorporation of many incorrect amino acids into the protein. In contrast,
if three nucleotides are inserted or deleted, there will be no shift in the
codon reading frame; however, there will be either one extra or one
missing amino acid in the final protein. Therefore, frameshift mutations
result in abnormal protein products with an incorrect amino acid
sequence that can be either longer or shorter than the normal protein.

7-Repeat expansion
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-
base-pair sequences, and a tetra nucleotide repeat is made up of 4-base-
pair sequences. A repeat expansion is a mutation that increases the
number of times that the short DNA sequence is repeated. This type of
mutation can cause the resulting protein to function improperly.
EXAMPLE:
Examples in this group include Fragile X syndrome, Friedreich's ataxia,
and myotonic dystrophy.
References:
www.evolution.berkeley.com
www.nature.com
www.brittanica.edu.com
www.csudh.edu