GEB 204

General Genetics and Genetic Analysis

Mutations
Lecture 13

Arindita Das
Lecturer
Department of Genetic Engineering and
Biotechnology
East West University
Gene Mutations

• Any Change in the nucleotide sequence/ DNA sequence of a gene

• May only involve a single nucleotide
• May be due to copying errors, chemicals, viruses, etc.
• Nucleotides/Bases may be added, missing, or changed
• Base Pair Substitutions
• Silent
• Missense – new protein (Amino Acid Substitutions)
• Nonsense – stop codon
• Base Pair Insertions and deletions
• Triplet Repeats
• Frameshift Mutations
 Gene Mutations

• KEY IDEA: A mutated gene will make a mutated protein

• Mutant proteins are trouble!
• They do not go where they are supposed to go
• They do not do what they are supposed to do

Types of gene mutation

➢Number of ways to classify gene mutations:

❖ Based on the molecular nature of the defect
❖ On the nature of the phenotypic effect-- amino acid sequence of the protein is altered or not
❖ Based on the causative agent of the mutation
❖ Base substitution
❖ Insertions & deletions
Base substitution:
❖ Simplest type of gene mutation
❖ Involves the alteration of a single nucleotide in the DNA
Base substitution is of two types:

Transition:
Purine is replaced with a purine

Pyrimidine is replaced with a pyrimidine

Transversions:
A purine is replaced by a pyrimidine or a pyrimidine is replaced by a purine
Insertions & deletions:

❖ 2nd major class of gene mutation

❖ Addition or the removal, respectively, of one or more nucleotide pair
❖ Usually changes the reading frame, altering all amino acids encoded by
codons following the mutation
❖ Also called as frame shift mutations
❖ Additions or deletions in the multiples of three nucleotides will lead to
addition or deletion of one or more amino acids
❖ These mutations are called in-frame insertions and deletions, respectively.
Mutations on the basis of the Phenotypic effects of mutations:

❖ Most common phenotype in natural populations of the organism is called as wild type
phenotype

❖ The effect of mutation is considered with reference to wild type phenotype

Forward mutation:
❖ a mutation that alters the wild type phenotype

Reverse mutation (reversion):

❖ a mutation that changes a mutant phenotype back in to the wild type
Missense mutation: a base is substituted that Nonsense mutation: changes a sense codon into a
alters a codon in the mRNA resulting in a nonsense codon. Nonsense mutation early in the
different amino acid in the protein product mRNA sequence produces a greatly shortened &
usually nonfunctional protein

TCA TTA TCA TGA

AGT AAT AGT ACT

UCA UUA
UCA UGA
Stop codon

Ser Leu Ser

Silent mutation: alters a codon but due to Neutral mutation: mutation that alters the amino
degeneracy of the codon, same amino acid acid sequence of the protein but does not change its
is specified function as replaced amino acid is chemically
similar or the affected aa has little influence on
protein function.
TCA TCG
CTT ATT
AGT AGC
GAA TAA

UCA CUU AUU

UCG
Leu Ile
Ser Ser
Loss of function mutations:
❖ Complete or partial loss of the normal function
❖ Structure of protein is so altered that it no longer works correctly
❖ Mutation can occur in regulatory region that affects transcription , translation or spilicing
of the protein
❖ Frequently recessive

Gain of function mutations:

❖ Produces an entirely new trait
❖ Causes a trait to appear in inappropriate tissues or at inappropriate times in
development
❖ Frequently dominant

Conditional mutations:
❖ Expressed only under certain conditions

Lethal mutations:
❖ Cause the death of the organism
Suppressor mutation:
❖ Suppresses the effect of other mutation
❖ Occurs at a site different from the site of original mutation
❖ Organism with a suppressor mutation is a double mutant
but exhibits the phenotype of un mutated wild type
❖ Different from reverse mutation in which mutated site is
reverted back into the wild type sequence
On the basis of Causative agent of mutation:

Spontaneous:
❖ Mutations that result from natural changes in DNA

Induced:
❖ Results from changes caused By
environmental chemicals & radiations
❖ Any environmental agent that increases the rate of mutation above
the spontaneous is called a mutagen such as chemicals & radiations