*Changes in the sequence of the DNA (or RNA)
*Ultimate source of VARIATION and NOVELTY in
evolution
Mutations
Types of mutations
According to size
Effect on gene function
Effect on DNA
Effect on protein
Direction
Types of mutations according to size:
- Point – single nucleotide or nucleotide pair; Single Nucleotide Polymorphisms (SNP’s)
- Segmental – several bp or more
Types of mutations based on effect on gene function:
- Loss of function – usually recessive
- Gain of function – usually dominant
Types of mutations based on effect on DNA:
- structural – change in nucleotide content
- spatial – change in the location of nucleotides
Types of structural mutations
a. substitution – change of 1 nucleotide for another
b. deletion – loss of 1 or more nucleotides
c. insertion – addition of 1 or more nucleotides
refers to either an insertion or deletion
Indel
Types of substitution mutations (2)
- transition – purine to purine or pyrimidine to pyrimidine
- transversion – purine to pyrimidine or pyrimidine to purine
Why is transition more likely despite there being more transversion pathways?
It is easier for a base to change into something with a similar structure.
Types of spatial mutations
a. inversion – 180 deg rotation or flip
b. translocation – movement to another region
Types of mutations based on effect on proteins
- silent
- nonsense
- missense
- neutral
- frameshift
Mutation where:
- no change in amino acid
– usually on 3rd codon position
– SYNONYMOUS
Silent
Mutation where:
– normal codon to a stop codon
– acts on pre termination codons
UGC (cys) to UGA (stop)
UAC (tyr) to UAG (stop)
Nonsense
Mutation where:
-There is change in amino acid transcribed
– alters protein function
- ex. sickle cell anemia
Missense
Mutation where:
– change in amino acid transcribed, but new
amino acid is similar functionally
– does NOT alter protein function
Neutral
Mutation where:
- caused by indel
- shift in reading frame (big clue)
Frameshift
Types of mutations based on direction:
- forward – wild type to abnormal phenotype
- Reverse or backward – abnormal to wild type
Origins of mutations
- spontaneous
- error-prone replication bypass
- errors in DNA repair
- induced
Repair mechanisms for mutations (4)
- photoreactivation
- excision repair
- mismatch repair
- SOS repair
Gene that experiences highest mutations; resembles functional genes but contain defects preventing expression
Pseudogene
Regions in the genome more prone to mutation than others
Hotspots
a. Triggered by high levels of DNA damage
b. Accumulation of ssDNA due to blocking of DNA polymerase at replication fork
due to error
c. Does not repair, it only allows for DNA replication to proceed
d. Allows DNA replication to bypass lesions or errors in DNA
e. Uses the recA protein
f. Error-prone system
SOS repair
a. Removal of damaged DNA by light-dependent enzyme
b. Present in E.coli
c. Encoded by phr gene
Photoreactivation
a. Excision of damaged part
b. Caused by DNA polymerase I
Excision repair
