By: Prof.

Mohamed El-Awady
Topics to be covered by the of the lecture

 1- Definition of mutations.

 2- Causes of mutations

 3-Types of mutations

 4- DNA REPAIR
 1- Definition of mutation

 Heritable change in the genetic material.

 Or, Permanent structural change of DNA.

Note that:
 Mutation

 Resulted in Various phenotypic effects

 Neutral
 Harmful

 Beneficial

 Most mutations are neutral

 More likely to be harmful than beneficial to

the individual
 More likely to disrupt function than
improve function
 2- CAUSES OF MUTATIONS

 Two causes of mutations

 Spontaneous mutations
 Resulted from abnormalities in biological
processes.
 Underlying cause lies within the cell.

 Induced mutations
 Caused by environmental agents.
 Cause originates outside of the cell.

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 Spontaneous Mutations

 Causes of spontaneous mutations

 Abnormalities in crossing over

 Aberrant segregation of chromosomes during meiosis
 Mistakes by DNA polymerase during replication
 Alteration of DNA by chemical products of normal
metabolic processes
 Integration of transposable elements
 Spontaneous changes in nucleotide structure

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 Note that:
 Spontaneous mutations are random events
 Not purposeful
 Mutations occur as a matter of chance
 Some individuals possess beneficial mutations
 Better adapted to their environment

 Increased chance of surviving and reproducing

 Natural selection results in differential reproductive

success
 The frequency of such alleles increases in the
population

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Rate of Spontaneous Mutations
 Induced mutations

 Induced mutations are caused by mutagens:

 Chemical substances or physical agents originating

outside of the cell

 Enter the cell and then alter the DNA structure

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Other terms
 Mutagens

 Tobacco products

 Nitrous Acid

 Mold Toxins

 X-rays

 Gamma Rays

 UV Radiation

 Some Artificial Sweeteners

 Common Causes of mutations

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 3- TYPES OF MUTATIONS
1- Classification based on size

 1- Chromosome mutations
 Changes in chromosome structure
 Changes in chromosome number (Genome mutations)

(we will study it in details in the practical session)

 2- Single-gene mutations (gene or point mutation)

 Relatively small changes in DNA structure
 Occur within a particular gene

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2-Classification based on the type of
molecular change
Types of point mutation
 Two types of base substitutions

 Transition
 Pyrimidine changed to another
pyrimidine
 e.g., C → T
 Purine changed to another
purine
 e.g., A → G

 Transversion
 Purines and pyrimidines are
interchanged
 e.g., A → C
 More rare than transitions 18
 Adenine
Transversion Transversion

Thymine Transition Cytosine

Transversion Transversion

Guanine
What happens when you get insertions or deletions of
bases in the DNA sequence?
* Usually you end up with a mess (Frameshift) !!!!

THE BIG FAT CAT ATE THE RAT AND GOT ILL

Deletion of one base

THE IGF ATC ATA TET HER ATA NDG OTI LL

 EFFECTS OF MUTATIONS

 Mutations within the coding sequence of a gene can have

various effects on the encoded polypeptide’s amino acid
sequence
 Silent mutations

 Missense mutations

Included neutral mutations

 Nonsense mutations

 Frameshift mutations

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 Silent mutations

 Amino acid sequence is not altered

 e.g., CCC → CCG (pro → pro)

 Genetic code is degenerate

 Alterations of the third base of a codon often do not

alter the encoded amino acid

 Phenotype is not affected

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 Missense mutations
 Amino acid sequence is altered
 e.g., GAA →GTA (glu → val)
 Phenotype may be affected

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 Neutral mutations

 Type of missense mutation

 Amino acid sequence is altered
 e.g., CTT →ATT (leu → ile)
 e.g., GAA →GAC (glu → asp)

 No detectable effect on protein function

 Missense mutations substituting an amino acid

with a similar chemistry to the original is likely to
be neutral

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 Nonsense mutations

 Normal codon is changed into a stop codon

 e.g., UAA → UAG (lys → stop)

 Translation is prematurely terminated

 Truncated polypeptide is formed

 Protein function is generally affected

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Types of base pair substitutions and mutations
Types of base pair substitutions and mutations
EFFECTS OF MUTATIONS

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29
 Note that:

 Mutations occasionally produce a polypeptide with

an enhanced ability to function
 Relatively rare

 May result in an organism with a greater likelihood

to survive and reproduce

 Natural selection may increase the frequency of

this mutation in the population

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 4- DNA REPAIR

 Most mutations are deleterious

 DNA repair systems are vital to the survival

 Bacteria possess several different DNA repair systems.

 Humans defective in a single DNA repair system may

manifest various disease symptoms

 e.g., Higher risk of skin cancer

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 Importance of DNA Repair

• DNA is the only biological macromolecule that is repaired.

All others are replaced.

• More than 100 genes are required for DNA repair, even in
organisms with very small genomes.

• Cancer is a consequence of inadequate DNA repair.

 Mechanisms of DNA Repair

 Direct repair
 Alkylguanine transferase
 Photoreactivation repair

 Excision repair
 Base excision repair
 Nucleotide excision repair
 Mismatch repair
 Recombination repair
 Living cells contain several DNA repair systems
Able to fix different types of DNA alterations

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1-Photoreactivation repair: reversal of UV
damage in prokaryotes
 2-Base excision repair (BER)

Takes advantage of the double-stranded (double information)

nature of the DNA molecule.

Four major steps:

1. Recognize damage.
2. Remove damage by excising part of one DNA strand.
3. The resulting gap is filled using the intact strand as the
template.
4. Ligate the nick.
 3-Nucleotide Excision Repair

• Corrects any damage that both distorts the DNA molecule

and alters the chemistry of the DNA molecule (pyrimidine
dimers, benzo[a]pyrene-dG adducts, cisplatin-DNA cross-
links) common in eukaryotes.
O
H3C
O H
NH NH2
O N
N NH
N O
5' HO N
O HO32N
CH Cl O N
H2N N OHNH
2
-GG-
N
HOPt H2N
NHPt OH H2N OH2 Pt N
O H2N Cl H2N O
O P O- N O HO N
O OH NH
O N
N
NH2
3'
 4-Mismatch Repair Enzymes

Nucleotide mismatches can be corrected after DNA synthesis!

Repair of nucleotide mismatches:

1. Recognize parental DNA strand (correct base) and daughter

strand (incorrect base)
NH2 Me
HN
H3C
Parental strand is methylated: N N N
N O N N

2. Replace a portion of the strand containing erroneous nucleotide

(between the mismatch and a nearby methylated site –up to 1000 nt)
5-Recombination
repair
DNA replication error