3. What are mutations?
- Any changes in the DNA sequence of
an organism is a mutation.
- DNA is made of a long sequence of
smaller units strung together. There
are four basic types of unit: A, T, G,
and C.
- Some parts of DNA are control
centers for turning genes on and off.
- some parts have no function.
- And some parts have a function that
we don't understand yet.
- Organisms have mechanisms such
as DNA repair to remove mutations.
4. What are mutations?
- Other parts of DNA are genes
that carry the instructions for
making proteins .
- Proteins are long chains of
amino acids.
- These proteins help build an
organism.
- Protein-coding DNA can be
divided into codons — sets of
three bases that specify an
amino acid or signal the end of
the protein.
6. A- Good or bad or neutral.
- A harmful mutation
Is a mutation that decreases the fitness of the organism.
- A beneficial mutation
Is a mutation that increases fitness of the organism, or which promotes
traits that are desirable.
- A neutral mutation
Has no harmful or beneficial effect on the organism. Such mutations occur
at a steady rate, forming the basis for the molecular clock.
8. C- Spontaneous or Induced Mutations
- Most mutations are spontaneous, rather than being induced
by a mutagen.
- Spontaneous mutation ; A mutation occurring in the absence
of mutagens, usually due to errors in the normal functioning
of cellular enzymes.
9. Spontaneous Mutations
These mutations can be caused by:
• Tautomerism – A base is changed by
the repositioning of a hydrogen atom,
altering the hydrogen bonding pattern
of that base resulting in incorrect base
pairing during replication.
• The ability of a molecule to exist in
more than one chemical form is called
tautomerism .
• All the four common bases of DNA (A,
G, C and T) have unusual tautomeric
forms, which are rare.
10. Spontaneous Mutations
- Depurination – In molecular genetics,
depurination is an alteration of DNA
in which the purine base (adenine or
guanine) is removed from the
deoxyribose sugar by hydrolysis of the
beta-N-glycosidic link between them.
- Loss of a purine base form an apurinic
site (AP site). where the sugar
phosphate backbone remains and the
sugar ring has a hydroxyl (-OH) group
in the place of the purine.
11. Spontaneous Mutations
• Deamination – Hydrolysis changes a normal base to an atypical
base containing a keto group in place of the original amine group.
12. Spontaneous Mutations
- Slipped strand mispairing -
Denaturation of the new strand
from the template during
replication, followed by
renaturation in a different spot
lead to insertions or deletions.
- (SSM) is a process that
produces mispairing of short
repeat sequences between the
mother and daughter strand
during DNA synthesis
13. Induced Mutations
• Ingredients that cause mutations
are called mutagens. Mutagen is
divided into three, namely:
1- Mutagenic chemicals like;
• Hydroxylamine NH2OH
• Base analogs (e.g. BrdU)
• Alkylating agents
• Agents that form DNA adducts
• DNA intercalating agents
• DNA crosslinkers
• Oxidative damage
14. Induced Mutations
Nitrous acid converts amine groups on A and C to diazo
groups, altering their hydrogen bonding patterns which
leads to incorrect base pairing during replication.
16. Induced Mutations
- Ultraviolet light is absorbed
by the nucleic acid bases,
and the resulting influx of
energy can induce chemical
changes.
17. Induced Mutations
- The most frequent photoproducts
are the consequences of bond
formation between adjacent
pyrimidines within one strand,
and, of these, the most frequent
are cyclobutane pyrimidine dimers
(CPDs).
- T CPDs are formed most readily,
followed by T-C or C-T; C-C dimers
are least abundant.
18. Induced Mutations
3- Mutagen biological substances.
suspected viruses and bakeries can
cause mutations. Of the virus that
can cause mutations is DNA.
19. D- Forward or Reverse Mutations
- In an organism when mutations created a change from
wild type to abnormal phenotype, then that type of
mutations are called forward mutations.
- Most mutations are of forward type.
- The forward mutations are often corrected by error,
correcting mechanism, so that an abnormal phenotype
changes into wild type phenotype. Such mutations are
called back or reverse mutations.
21. Point mutations
- Point mutations also called
Single base substitutions
are single nucleotide base
changes in a gene's DNA
sequence.
- It exchange a single
nucleotide for another.
- These changes are classified
as transitions or
transversions.
22. Point mutations
- Most common is the transition
that exchanges a purine for a
purine (A ↔ G) or a
pyrimidine for a pyrimidine, (C
↔ T).
- Less common is a transversion,
which exchanges a purine for a
pyrimidine or a pyrimidine for
a purine (C/T ↔ A/G).
23. Point mutations
- Point mutations that
occur within the protein
coding region of a gene
may be classified into
three kinds, depending
upon what the
erroneous codon codes
for:
• Silent mutations: which
code for the same amino
acid.
• Missense mutations:
which code for a different
amino acid.
• Nonsense mutations:
which code for a stop and
can truncate the protein.
25. frameshift mutations
- Frameshift mutation is a
mutation caused by add or
remove one or more DNA
bases of nucleotides that is
not evenly divisible by three
from a DNA sequence.
- Insertion or deletion
mutations cause frameshift
mutations.
26. frameshift mutations
• Addition or
deletion of one or
two bases results in
a new sequence of
codons which may
code for entirely
different amino
acids. This results in
a drastic change in
the protein
synthesized.
27. DNA Repair
• Cells have developed a number
of systems designed to repair
DNA damage and correct
mutations.
1- Photoreactivation
- For Repair Thymine Dimers by A
brief exposure to blue light
following UV exposure can
reverse the effects of the UV
radiation.
28. DNA Repair
• An enzyme called
photolyase or
photoreactivation
enzyme (PRE), which
cleaves the covalent
bonds linking the
thymine dimers using
the energy from a
DNA Repair Pathway. This flow chart shows one way that damaged
photon of blue light. DNA is repaired in E. coli bacteria.
29. DNA Repair
• 2- Base excision repair
The damaged or inappropriate base
is removed from its sugar linkage and
replaced. These are glycosylase
enzymes which cut the base-sugar
bond.
• 3- Nucleotide excision repair
- This system works on DNA damage
which is "bulky" and creates a block
to DNA replication and transcription.
- (UV-induced dimers and some kinds
of chemical adducts).
- It probably recognizes not a specific
structure but a distortion in the
double helix.
30. DNA Repair
4- Recombinational (daughter-strand
gap) repair
- This is a repair mechanism which
promotes recombination to fix the
daughter-strand gap--not the dimer--and
is a way to cope with the problems of a
non-coding lesion persisting in DNA.
- Double Strand Break (DSB) Repair.
Shown is an overview of the main steps
and factor requirements for DNA DSB
repair by homologous recombination (left)
and non-homologous end-joining (right).
31. DNA Repair
• Mismatch repair
- This process occurs after DNA replication as a
last "spellcheck" on its accuracy.
- In E. coli, it adds another 100-1000-fold
accuracy to replication.
- It is carried out by a group of proteins which
can scan DNA and look for incorrectly paired
bases (or unpaired bases) which will have
aberrant dimensions in the double helix.
- The incorrect nucleotide is removed as part
of a short stretch and then the DNA
polymerase gets a second try to get the right
sequence.
example: uracilglycosylase--enzyme which removes uracil from DNA.Several proteins are involvedin this process (in prokaryotes these are the products of the 'uvr' genes, for 'UV repair').
