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Transcript of Mutations
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Mutation
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Definition of a Mutation
• Any change in genetic material.
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What are Mutations• Any permanent random chemical change
in either:– the DNA (Gene Mutation)
– or the genetic makeup of a cell (Chromosome Mutation)
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Mutations- how often?
• Mutations occur all the time. • In Humans – each gene mutates on average
once in every 1,000,000 to 100,000,000 replications.
• We have about 25,000 genes in each cell• So on average – each person in the room
has one mutated gene (that is one gene that neither of their parents had).
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The effects of Mutations
• If a mutation occurs it can cause anything from no effect (silent mutation) to a lethal effect.
• Good or Bad mutations. If the mutation results in a phenotype that is of benefit to the individual, then it will be considered a good mutation.
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Mutations and Evolution
• Genetic variation comes from 1 Independent Assortment 2 Crossing over (recombination) 3 Mutations.
• The first two just mix the genes up.
• Only mutations can create new alleles. • All three assist a species to evolve!
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Definitions and Terminology
• Microevolution– Changes within populations or species in
gene frequencies and distributions of traits
• Macroevolution– Higher level changes, e.g. generation of
new species or higher–level classification
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Gene
• Section of a chromosome that encodes the information to build a protein
• Location is known as a “locus”
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Allele
• Varieties of the information at a particular locus• Every organism has two alleles (can be same or different) • No limit to the number of alleles in a population
An allele is a viable DNA coding that occupies a given locus (position) on a chromosome.
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Genotype
• Genetic information contained at a locus• Which alleles are actually present at a
locus
• Example: – Alleles available: R and W– Possible genotypes:
• RR, RW, WW
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Phenotype
• Appearance of an organism
• Results from the underlying genotype
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Phenotype
• Example 1:
– Alleles R (red) and W (white), codominance– Genotypes: RR, RW, WW– Phenotypes: Red, Pink, White
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Phenotype
• Example 2:
– Alleles R (red) and w (white), simple dominance– Genotypes: RR, Rw, ww– Phenotypes: Red, Red, white
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What Are Mutations?What Are Mutations?
• Changes in the nucleotide sequence of DNA
• May occur in somatic cells (aren’t passed to offspring)
• May occur in gametes (eggs & sperm) and be passed to offspring
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What Causes Mutations?• There are two ways in which DNA can
become mutated:– Mutations can be inherited.
• Parent to child
– Mutations can be acquired.• Environmental damage• Mistakes when DNA is copied
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What are the other factors?
• These factors may include: radiation, chemical exposures, UV light (sunlight)
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• Not necessarily harmful!– Dependent on: 1) nature of mutation
2) environment
• Spontaneous– occur randomly throughout genome– rates: 10-6 - 10-4 /gene/cell
• Reversible
• Many mutations are repaired by enzymes
Are Mutations Helpful or Harmful?
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• Some type of skin cancers and leukemia result from somatic mutations
• Some mutations may improve an organism’s survival (beneficial)
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Significance of Mutations• Most are neutral
• Eye color• Birth marks
• Some are harmful• Sickle Cell Anemia• Down Syndrome
• Some are beneficial• Sickle Cell Anemia to Malaria• Immunity to HIV
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Classification of
mutation types
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Classification of mutation typesBased on
• Effect on structure
• Effect on function
• Effect on fitness
• By inheritance
• Pattern of inheritance
• By impact on protein sequence
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Classification of mutation typesEffect on structure
• The Mutations which alters the structure of the genes
These can be classified as:i. Small-scale mutations Those affecting a small gene in one or a few
nucleotides
ii. Large-scale mutations in chromosomal structure, including
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Small-Scale MutationsGene Mutations
• Change in the nucleotide sequence of a gene
• May only involve a single nucleotide
• May be due to copying errors, chemicals, viruses, etc.
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Types of Gene Mutations
• Include:
–Point Mutations
–Insertions
–Deletions
–Frameshift
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Point Mutation• often caused by
– chemicals or – malfunction of DNA replication, – exchange a single nucleotide for another.
These changes are classified as transitions or transversions• Transition is the exchange of
a purine for a purine (A ↔ G) or
a pyrimidine for a pyrimidine, (C ↔ T). • A transition can be caused by nitrous acid, base mis-pairing, or
mutagenic base analogs.• This is the most common
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Point Mutation• often caused by
– chemicals or – malfunction of DNA replication, – exchange a single nucleotide for another.
These changes are classified as transitions or transversions
Less common is a transversion, which exchanges
a purine for a pyrimidine or
a pyrimidine for a purine (C/T ↔ A/G).
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Point Mutation
It can be reversed by another point mutation,•in which the nucleotide is changed back to its original state (true reversion) •Point mutations that occur within the protein coding region of a gene may be classified into three kinds:
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.
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Point Mutation
Silent mutations do not result in a change to the amino acid sequence of a protein.
These are also treated as evolutionarily neutral Mutations as they do not alter protein function.
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Point Mutation
• a change in a base pair does not result in a change in the sequence of amino acids in a protein
Silent mutations
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Point MutationMissense Mutation
in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid.
This renders the resulting protein nonfunctional.
Such mutations are responsible for diseases such as Epidermolysis bullosa, sickle-cell disease.
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Point Mutation
Defective protein glycosylation in patients with cutis laxa syndrome
Missense Mutation in Kindler Syndrome
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Point MutationNonsense mutation
in which a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product.
The effect of a nonsense mutation depends on how much of the protein is lost.
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Point Mutation• Nonsense Mutation in Kindler Syndrome
(a)Extensive atrophy on the trunk;
(b)Mottled hyperpigmentation in the right axilla;
(c)cigarette-paper-like atrophy on the dorsal aspects of the hands;
(d)mild palmoplantar keratoderma.
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Types of Gene Mutations
• Include:
–Point Mutations
–Insertions
–Deletions
–Frameshift
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Gene MutationsSmall-scale mutations
Insertions
• add one or more extra nucleotides into the DNA. • caused by transposable elements,
or errors during replication of repeating elements (e.g. AT repeats).
• Alter reading frame• which can significantly alter the gene product.
Insertions can be reverted by excision of the transposable element.
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Gene MutationsSmall-scale mutations
Insertions
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Gene MutationsSmall-scale mutations
Insertions in Desmoplakin
linical pictures showing the striated keratoderma on (a)palm and (b)sole of the patient and (c)(d) the woolly hair phenotype.
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Types of Gene Mutations
• Include:
–Point Mutations
–Insertions
–Deletions
–Frameshift
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Gene MutationsSmall-scale mutations
Deletions• remove one or more nucleotides from the DNA.
Like insertions, • alter the reading frame of the gene. • irreversible mutations• producing a non-functional protein.
• Deletion of a number of base pairs that is not evenly divisible by three will lead to a frameshift mutation
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Gene MutationsSmall-scale mutations
Deletions
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Gene MutationsSmall-scale mutations
Deletions
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Gene MutationsSmall-scale mutations
DeletionsReal examples of deletion mutations which cause diseases. (a) Deletion of "T" from the sequence
"TTTTT" in the CFTR gene. (b) Deletion of "AT" from the sequence
"ATAT" in the CFTR gene. (c) Deletion of "TTG" from the sequence
"TTGTTG" in the FIX gene. (d) Deletion of "ATAG" from the sequence
"ATAGATAG" in the APC gene.
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Gene MutationsSmall-scale mutations
Deletions
Deletion Mutation in Keratin 5 Causing the Removal of 5 Amino Acids and Elevated Mutant mRNA Levels in Dowling–Meara Epidermolysis Bullosa Simplex
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Types of Gene Mutations
• Include:
–Point Mutations
–Insertions
–Deletions
–Frameshift
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Frameshift Mutation
• Inserting or deleting one or more nucleotides
• Changes the “reading frame” like changing a sentence
• Proteins built incorrectly
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Frameshift Mutation
• Original:
–The fat cat ate the wee rat.• Frame Shift (“a” removed):
– The fat caa tet hew eer at.
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Frameshift Mutation
A frameshift mutation (framing error) • caused by indels, ie. insertion or deletion of a
number of nucleotides that is not evenly divisible by three from a DNA sequence.
• Resulting in a completely different translation from the original.
• Frameshift mutations frequently result in severe genetic diseases such as Tay-Sachs disease.
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Amino Acid Sequence Changed
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Gene MutationsSmall-scale mutations
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Classification of mutation typesBased on
• Effect on structure
• Effect on function
• Effect on fitness
• By inheritance
• Pattern of inheritance
• By impact on protein sequence
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Classification of mutation typesEffect on structure
• The Mutations which alters the structure of the genes
These can be classified as:i. Small-scale mutations Those affecting a small gene in one or a few
nucleotides
ii. Large-scale mutations in chromosomal structure, including
![Page 52: Mutations](https://reader035.fdocuments.in/reader035/viewer/2022062712/563db9c6550346aa9a9fcc80/html5/thumbnails/52.jpg)
• May Involve:– Changing the structure of
a chromosome
– The loss or gain of part of a chromosome
Large-Scale MutationsChromosaome Mutations
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Chromosome Mutations
• Five types exist:–Deletion
–Inversion
–Translocation
–Nondisjunction
–Duplication
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Deletion
• Due to breakage• A piece of a chromosome is lost
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Inversion
• Chromosome segment breaks off
• Segment flips around backwards
• Segment reattaches
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Duplication
• Occurs when a gene sequence is repeated
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Translocation
• Involves two chromosomes that aren’t homologous
• Part of one chromosome is transferred to another chromosomes
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Translocation
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Nondisjunction
• Failure of chromosomes to separate during meiosis
• Causes gamete to have too many or too few chromosomes
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Chromosome Mutation Animation
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Chromosome Mutations
• Down Syndrome– Chromosome 21 does
not separate correctly.– They have 47
chromosomes in stead of 46.
– Children with Down Syndrome develop slower, may have heart and stomach illnesses and vary greatly in their degree of inteligence.
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Chromosome Mutations
• Cri-du-chat– Deletion of material on 5th
chromosome– Characterized by the cat-like
cry made by cri-du-chat babies
– Varied levels of metal handicaps
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Sex Chromosome Abnormalities
• Klinefelter’s Syndrome– XXY, XXYY, XXXY– Male– Sterility– Small testicles– Breast enlargement
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Sex Chromosome Abnormalities
• XYY Syndrome– Normal male traits– Often tall and thin– Associated with antisocial and behavioral
problems
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Sex Chromosome Mutations
• Turner’s Syndrome– X– Female– sex organs don't
mature at adolescence
– sterility– short stature
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Sex Chromosome Mutations
• XXX– Trisomy X– Female– Little or no visible differences– tall stature– learning disabilities– limited fertility
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Classification of mutation typesBased on
• Effect on structure
• Effect on function
• Effect on fitness
• By inheritance
• Pattern of inheritance
• By impact on protein sequence
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Classification of mutation typesEffect on function
• Loss-of-function mutations
• Gain-of-function mutations
• Dominant negative mutations
• Lethal mutations
• A back mutation or reversion
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Classification of mutation typesEffect on function
• Loss-of-function mutations
• results in gene product having less or no function.
• When the allele has a complete loss of function (null allele) it is often called an amorphic mutation.
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Classification of mutation typesEffect on function
• Gain-of-function mutations
• changes the gene product such that it gains a new and abnormal function.
• These mutations usually have dominant phenotypes.
• Often called a neomorphic mutation.
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Effect on function• Dominant negative mutations
also called antimorphic mutations•have an altered gene product that acts antagonistically to the wild-type allele. •These mutations usually result in an altered molecular function (often inactive.
•In humans, Marfan syndrome is an example• In this the defective glycoprotein product of the
fibrillin gene (FBN1) antagonizes the product of the normal allele.
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Classification of mutation typesEffect on function
• Lethal mutations
are mutations that lead to the death of the organisms which carry the mutations
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Classification of mutation typesEffect on function
• A back mutation or reversion
is a point mutation that restores the original sequence and hence the original phenotype.
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Classification of mutation typesBased on
• Effect on structure
• Effect on function
• Effect on fitness
• By inheritance
• Pattern of inheritance
• By impact on protein sequence
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Classification of mutation typesEffect on fitness
Mutations are either harmful or beneficial
• Harmful mutation
that decreases the fitness of the organism.
• Beneficial mutation
increases fitness of the organism, or which promotes traits that are desirable.
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Classification of mutation typesEffect on fitness
• Neutral mutation:has no harmful or beneficial effect on the organism.
• Deleterious mutation:has a negative effect on the phenotype, and thus decreases the fitness of the organism.
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Classification of mutation typesEffect on fitness
• Advantageous mutation:has a positive effect on the phenotype, and thus increases the fitness of the organism.
• Nearly neutral mutation:may be slightly deleterious or advantageous,
although most nearly neutral mutations are slightly deleterious
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Classification of mutation typesBased on
• Effect on structure
• Effect on function
• Effect on fitness
• By inheritance
• Pattern of inheritance
• By impact on protein sequence
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Classification of mutation types
Mutations by inheritance
• inheritable generic in pro-generic tissue or cells on path to be changed to gametes.
• non inheritable somatic (eg, carcinogenic mutation)
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Classification of mutation typesBased on
• Effect on structure
• Effect on function
• Effect on fitness
• By inheritance
• Pattern of inheritance
• By impact on protein sequence
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Classification of mutation typesMutations by pattern of inheritanceThe human genome contains two copies of each gene – a paternal and a maternal allele.
Heterozygous mutation: a mutation of only one allele.
Homozygous mutation:an identical mutation of both the paternal and
maternal alleles.
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Classification of mutation typesMutations by pattern of inheritanceThe human genome contains two copies of each gene – a paternal and a maternal allele.
Compound heterozygous:comprises two different mutations in the
paternal and maternal alleles.
Wildtype or homozygous non-mutated:organism is one in which neither allele is
mutated. (Just not a mutation)
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Classification of mutation typesBased on
• Effect on structure
• Effect on function
• Effect on fitness
• By inheritance
• Pattern of inheritance
• By impact on protein sequence
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Classification of mutation typesMutation by impact on protein sequence
• Frameshift mutation
• Missense mutations
• Neutral mutation
• Nonsense mutation
• Silent mutations
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Classification of mutation typesMutation by impact on protein sequence•Frameshift mutation:
is a mutation caused by insertion or deletion of a number of nucleotides that is not evenly divisible by three from a DNA sequence.
Due to the triplet nature of gene expression by codons, the insertion or deletion can disrupt the reading frame, or the grouping of the codons, resulting in a completely different translation from the original.
as a result more altered the protein produced is.
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Classification of mutation typesMutation by impact on protein sequence•Missense mutations
mutations are types of point mutations change in single nucleotide is changed to cause
substitution of a different amino acid.
This in turn can render the resulting protein nonfunctional.
these are responsible for diseases such as Epidermolysis bullosa, sickle-cell disease.
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Classification of mutation typesMutation by impact on protein sequence•Neutral mutation
occurs in an amino acid codon which results in the use of a different, but chemically similar, amino acid.
This is similar to a silent mutation, where a codon mutation may encode the same amino acid
for example, a change from AUU to AUC will still encode leucine, so no discernible change occurs.
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Classification of mutation typesMutation by impact on protein sequence
•Nonsense mutation
is a point mutation in a sequence of DNA that results in
a premature stop codon, or a nonsense codon in the transcribed
mRNA,
and possibly a truncated, and often nonfunctional protein product.
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Classification of mutation typesMutation by impact on protein sequence•Silent mutations
do not result in a change to the amino acid sequence of a protein.
may occur in a region that does not code for a protein,
or may occur within a codon in a manner that does not alter the final amino acid sequence.
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Classification of mutation typesMutations Based on
• Effect on structure
• Effect on function
• Effect on fitness
• By inheritance
• Pattern of inheritance
• By impact on protein sequence
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Causes of
mutation
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Causes of mutation
Two classes of mutations are
• Spontaneous mutations (molecular decay) and
• Induced mutations caused by mutagens
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Causes of mutationSpontaneous mutations (molecular decay)
Spontaneous mutations on the molecular level include:
• Tautomerism
• Depurination
• Deamination
• Transition
• Transversion
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Causes of mutationSpontaneous mutations (molecular decay)
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.
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The Existence of a molecule in a keto and a enol form is known as tautomerisum.
This is due to a chemical reaction called tautomerization. Commonly this reaction results in the formal migration of a hydrogen atom or proton, accompanied by a switch of a single bond and adjacent double bond.
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Causes of mutationSpontaneous mutations (molecular decay)
Depurination
Loss of a purine base (A or G) from the deoxyribose sugar by hydrolysis of the beta-N-glycosidic link between them.
The sugar phosphate backbone remains and the sugar ring has a hydroxyl (-OH) group in the place of the purine.
Studies estimate that as many as 10,000 purines are lost this way each day in a typical human cell,
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Causes of mutationSpontaneous mutations (molecular decay)
Depurination
One of the main causes of depurination is the presence of endogenous metabolites in cell undergoing chemical reactions.
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Causes of mutationSpontaneous mutations (molecular decay)
Deamination
Deamination is the removal of an amine group from a molecule.
Hydrolysis changes a normal base to an atypical base containing a keto group in place of the original amine group. Example: C → U and A → HX (hypoxanthine), which can be corrected by DNA repair mechanisms;
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Causes of mutationSpontaneous mutations (molecular decay)
TransitionTransition is the exchange of
a purine for a purine (A ↔ G) or a pyrimidine for a pyrimidine, (C ↔ T).
A transition can be caused by nitrous acid, base mis-pairing, or mutagenic base analogs.
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Causes of mutationSpontaneous mutations (molecular decay)
Transversion
transversion, which exchanges
a purine for a pyrimidine or
a pyrimidine for a purine (C/T ↔ A/G).
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Causes of mutation
Induced mutations are mainly caused by mutagens such as
• Chemicals
• Radiations
• Viral infections
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Causes of mutationChemical Mutagens –
can be divided into two classes:
Class I Mutagens: which can cause mutations to both replicating and non replicating DNA.
class II mutagens: which affect replicating nucleic acids. molecules look like nucleic acid; hence they are incorporated into the replicating DNA molecule.
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Causes of mutationChemical Mutagens –
can be divided into two classes:
Class I Mutagens: • Hydroxylamine
• Nitrous acid
• Alkylating agent
• DNA crosslinkers
• Oxidative damage
• Agents that form DNA adducts
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Causes of mutation
• reacts with pyrimidine bases.
• Its effect is strong on cytosine
• It breaks and removes pyrimidine ring of uracil thus producing phosphoribosyl urea and 5' isoxasolone with cytosine,
• finally produces hydroxyl amino (-NOH) derivative, which might be responsible for base pair change (GC-AT pair).
Class I Chemicals Mutagens:Hydroxylamine NH2OH
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Causes of mutation
• Mutations induced by hydroxylamine cannot be reversed with hydroxylamine.
Class I Chemicals Mutagens:Hydroxylamine NH2OH
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Causes of mutation
• very potent mutagen that acts directly on either replicating or non replicating DNA
• by oxidation or deamination of the bases that contain amino groups (adenine-A, guanine-G and cytosine-C).
• Conversion of the amino groups to keto groups
changes the hydrogen bonding potential of the bases.
Class I Chemicals Mutagens:Nitrous Acid (HNO2)
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Causes of mutation
• Adenine is deaminated to hypoxanthine, • Which pairs with cytosine in the place of thymine.
• Since the deamination of adenine leads to AT. GC transition, nitrous acid induces transitions in both directions.
Class I Chemicals Mutagens:Nitrous Acid (HNO2)
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Causes of mutation
• Cytosine is deaminated to uracil, which now pairs with adenine in the place of guanine.
• Deamination of cytosine results in CC. AT transitions,
Class I Chemicals Mutagens:Nitrous Acid (HNO2)
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Causes of mutation
• Deamination of guanine has zero effect, as deaminated guanine also pairs with cytosine.
Class I Chemicals Mutagens:Nitrous Acid (HNO2)
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Causes of mutation
• Nitrous acid also causes interstrand cross-linking of DNA.
• The DNA strands fail to separate and there is no DNA duplication, which is lethal or deleterious.
Class I Chemicals Mutagens:Nitrous Acid (HNO2)
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Causes of mutation
• These agents can mutate both replicating and non-replicating DNA.
• a base analog can only mutate the DNA when the analog is incorporated in replicating the DNA.
• They induce all types of mutations, • transitions, transversions, frameshifts and • even chromosome aberrationsdepending on the specific alkylating agent.
Class I Chemicals Mutagens:Alkylating agent
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Causes of mutation
• In mutagenesis,alkylating agents involves the transfer of methyl or ethyl group to the bases such that their base-pairing potentials are altered and transitions result.
Class I Chemicals Mutagens:Alkylating agent
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Causes of mutation
• carry one, two or more alkyl groups in reactive form• These are capable of being transferred to other
molecules where electron density is high.• They are most powerful mutagens. Examples are:
Class I Chemicals Mutagens:Alkylating agent
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Causes of mutation
• These chemicals attack different reactive groups. • reactive atoms for alkylation are the N7 of guanine
and the N3 of adenine.
• Alkylation at these positions will distort the double helix. Such distortions can be repaired by an.
• The DNA becomes distorted as a result and the ability of proteins to recognize and bind correctly is hindered.
Class I Chemicals Mutagens:Alkylating agent
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Causes of mutation
• Alkylation can also occur at oxygen atoms: • O6 of guanine and • O4 of thymine.
This will result in mispairing of base pairs but does not generate major distortions..
O-6-ethylguanine will pair with thymine and O-4-ethylthymine will pair with guanine.
Class I Chemicals Mutagens:Alkylating agent
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Causes of mutationClass I Chemicals Mutagens:Alkylating agent
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• Nitrous acid (HNO2)– causes deamination of A, C, and G– point mutations
• Alkylating agents– EMS (ethyl methane sulfonate),EES (ethyl ethane
sulfonate) mustard gas (sulfur mustard), nitrogen mustard
• cause misspairing and/or depurination• frameshifts
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Causes of mutationChemical Mutagens –
can be divided into two classes:
Class I Mutagens: • Hydroxylamine
• Nitrous acid
• Alkylating agent
• DNA crosslinkers
• Oxidative damage
• Agents that form DNA adducts
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Causes of mutation
• A DNA adduct is a piece of DNA covalently bonded to a (cancer-causing) chemical.
Examples of DNA adducts are:acetaldehyde
(a major component of cigarette smoke)
Etheno adducts
1-Nitropyrene
• This has shown to be the start of a cancerous cell, or carcinogenesis.
Class I Chemicals Mutagens:Agents that form DNA adducts
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Causes of mutationClass I Chemicals Mutagens:Agents that form DNA adducts
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Causes of mutationChemical Mutagens –
can be divided into two classes:
Class I Mutagens: • Hydroxylamine
• Nitrous acid
• Alkylating agent
• DNA crosslinkers
• Oxidative damage
• Agents that form DNA adducts
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Causes of mutation
• Chemical agents responsible for crosslinks in DNA
• Crosslinks in DNA occur when various exogenous or endogenous agents react with two different positions in the DNA.
Class I Chemicals Mutagens:DNA Crosslinkers
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Causes of mutation
• This can either occur in same strand (intrastrand crosslink) or
opposite strands(interstrand crosslink)
• DNA replication is blocked by crosslinks, which causes replication arrest and cell death if the crosslink is not repaired.
Class I Chemicals Mutagens:DNA Crosslinkers
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Causes of mutation
These are two types: Exogenous Crosslinkers
Endogenous Crosslinkers
Class I Chemicals Mutagens:DNA Crosslinkers
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Causes of mutation
Exogenous CrosslinkersClass I Chemicals Mutagens:
• Alkylating agents such as1, 3-bis(2-chloroethyl)-1-nitrosourea andNitrogen mustard
which are used in chemotherapy can cross link with DNA at N7 position of guanine on the opposite strands forming interstrand crosslink.
Cisplatin Mostly it acts on the adjacent N-7 guanine forming 1, 2 intrastrand crosslink.
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Causes of mutation
Endogenous CrosslinkersClass I Chemicals Mutagens:
• Nitrous acid formed in the stomach dietary source nitrites. It induces formation of interstrand DNA crosslink at aminogroup of guanine at the CG sequences.
• Reactive chemicals such as malondialdehyde which are formed endogenously as the product of lipid peroxidation.
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Causes of mutation
Endogenous CrosslinkersClass I Chemicals Mutagens:
• Psoralens are natural compounds (furocoumarins) present in plants.
• These compounds get activated in the presence of UV.
• The crosslinking reaction by Psoralens targets TA sequences in DNA and linking one base of the DNA with the one below it.
• Psoralen adducts cause replication arrest and is used in the treatment of psoriasis and vitiligo.
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Causes of mutation
Endogenous CrosslinkersClass I Chemicals Mutagens:
• Aldehydes such as acrolein and crotonaldehyde found in tobacco smoke or automotive exhaust can form DNA interstrand crosslinks in DNA.
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Causes of mutationChemical Mutagens –
can be divided into two classes:
Class I Mutagens: • Hydroxylamine
• Nitrous acid
• Alkylating agent
• DNA crosslinkers
• Oxidative damage
• Agents that form DNA adducts
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Causes of mutationClass I Chemicals Mutagens:
Oxidative damageOxidative damage can be caused by
superoxide radicals, hydrogen peroxide, or hydroxide radicals.
The most important type of oxidative damage is the formation of 8-oxo-guanine which will pair with adenine and generate transversions.
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Causes of mutationClass I Chemicals Mutagens:
Oxidative damage.
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Causes of mutationClass I Chemicals Mutagens:
Oxidative damage.
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Causes of mutationClass I Chemicals Mutagens:
Oxidative damage.
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Causes of mutationChemical Mutagens –
can be divided into two classes:
Class II Mutagens: The molecules of class II mutagens look like nucleic
acid; hence they are incorporated into the replicating DNA molecule.
• Base analogs
• Acridine dyes
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Causes of mutationClass II- Chemical Mutagens:–
Base analogs
• have a structure similar to the normal bases
• they are metabolized and incorporated into DNA during replication.
• And that they increase the frequency of mis-pairing and thus cause mutation.
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Causes of mutationClass II- Chemical Mutagens:–
Base analogs
• 5-bromo-uracil
• 2-aminopurine
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Causes of mutationClass II- Chemical Mutagens:–
Base analogs
• 5-bromo-uracil
This analogue tautomerizes more readily than thymine. As a result, it will pair with guanine more frequently. The result is a TA -> CG transition.
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Causes of mutationClass II- Chemical Mutagens:–
Base analogs
• 2-aminopurine
This analogue normally pairs with thymine but when it is protonated, it will pair with cytosine. The result is an AT -> GC transition.
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Causes of mutationClass II- Chemical Mutagens:–
Base analogs
• 2-aminopurine
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Causes of mutationClass II- Chemical Mutagens:–
Acridine dyes
• They bind directly to the DNA by using their positive charge.
• Positively charged acridines intercalate or sandwich themselves between the stacked base pairs in DNA.
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Causes of mutationClass II- Chemical Mutagens:–
Acridine dyes • Acridine dyes separate two bases by 6.8 A, thus a
base will be missed.
• Acridine dyes can insert or delete only one base pair in DNA, and thus result in frameshift mutations.
• The examples of this class of mutagens are • nitrous acid (HNO2), • hydroxylamine, • hydrazine, H2O2 etc.
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Causes of mutation
Induced mutations are mainly caused by mutagens such as
• Chemicals
• Radiations
• Viral infections
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Causes of mutation
Induced mutations are mainly caused by mutagens such as
• Chemicals
• Radiations
• Viral infections
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• UV radiation produces pyrimidine problems– bonds form between two adjacent thymines
on one strand • leads to deletion of two bases
– cytosines converted to cytosine hydrate• leads to mispairing of bases
– FRAMESHIFTS
Causes of mutationInduced mutations
Radiations
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Causes of mutationInduced mutations
Radiations
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• Radiation– UV Rays (Sun)
Two nucleotide bases in DNA – cytosine and thymine – are most vulnerable to radiation that can change their properties.
UV light can induce adjacent thymine bases in a DNA strand to pair with each other, as a bulky dimer.
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Ionizing Radiation• X-rays, gamma rays, cosmic rays
– induce point mutations – induce gross structural changes in
chromosomes through breakage
Causes of mutationInduced mutations
Radiations