Definition and Classification of Mutations

Biology I

Hayder A Giha

Mutations • Mutations result as consequences of alteration

of the nucleotide sequence or number.• There are TWO major types of mutations:a. Chromosomal mutation b. Genetic mutation • The chromosomal mutations are eitheri. Numerical ii. Structural • Here we are going to study the genetic

mutations

Genetic mutations • Change of a single nucleotide in a gene and the

corresponding mRNA, known as point mutation(single base change or base substitution).

• It is a Transition point mutation if a purinenucleotide is replaced by a purine or apyrimidine is replaced by a pyrimidine.

• It is a Transversion if a purine is replaced by a pyrimidine or vise versa

• There are 3 types of point mutation based on the consequences on the protein product:

1. Silent mutation (also known as synonymous substitution): The codon contain the changed base code for the same amino acid encoded by the original codon e.g. serine is encoded by UCA changed codon UCU also code for serine, (due to the degeneracy of the genetic code).

Other types of point mutation • Missense mutation (a type of

nonsynonymous substitution): codoncontaining the changed base code for different amino acid e.g. Glycine (Gly) encoded by GGC, changed 1st

base result in AGC codon which code for serine (Ser) amino acid. The resulting protein could be acceptable - neutral mutation (functions normally e.g. Hb Hikari), partially acceptable (work but less efficient e.g HbS) or not acceptable (not functioning at all, e.g. Hb M).

Other types of point mutation • None-sense mutation: Codon contains the altered

base changed to stop codon (UAA, UAG or UGA), that leads to premature termination of protein synthesis and results in shorter (or truncated) proteine.g. lysine (Lys) codon is AAG, if the 1st base change to U, it becomes UAG, which do not code for any amino acid (stop codon or non-sense codon).

4. Other mutationsA. Trinucleotide repeats expansion: - The normally present tandem

(cyclical) repeats of trinucleotidemight be amplified (multiplied) in number, leading to gene expansion.

- If these triplet copies are in a coding region of a gene, the product proteinwill have several extra copies of one amino acid, that makes the proteinunstable and might lead to proteinaggregates as happened in some neurological diseases.

- If such expansion happed in a non-coding region, that might lead to reduction of the product protein.

4. Other mutationsA. Splice site mutation: mutation at splice site

might result in alteration of size and contentof an intron, resulting in aberrant (abnormal) protein.

Other mutationsC. Frame shift mutation: - If one or two nucleotides are added to or deleted

from a coding region of a gene, that results in frame shift after the site of insertion or deletionresult in alteration of sequence of all remaining nucleotides, since there is no overlapping or punctuation in the reading of the mRNA.

Other mutationsC. Frame shift mutation: - The product protein before the site of insertion or

deletion will be normal protein after it will be garbled protein with different amino acids, or truncated protein if the shift results in creation of stop codon pre-maturely.

- If 3 nucleotides togther as a triplet are inserted or deleted, that results in a protein with one extra or with one less amino acid, but with no frame shift.