Russell
Chapter 7 - DNA Mutation, DNA Repair, and
Transposable Elements
DNA Mutation
Mutations Defined
● Mutation: the process by which the sequence of base pairs in a DNA molecule are
altered
● Mutant cell: cell with a mutation
● Somatic mutation: when a mutation happens in a somatic cell
○ Affects the individual in which the mutation occurs
○ Not passed onto the succeeding generation
● Germ-line mutation: when a mutation happens in a reproductive cell (gamete)
○ Transmitted by the gametes to the next generation
○ Individual with the mutation in somatic + germ-line cells is produced
● Quantitative measure of occurance of mutations
○ Mutation rate: probability of a particular kind of mutation as a function of time
■ e.g. number of mutations per nucleotide pair per generation
■ e.g. number of mutations per gene per generation
○ Mutation frequency: number of occurances of a particular kind of mutation,
expressed as the proportion of cells/individuals in a population
■ e.g. number of mutations per 100.000 organisms
■ e.g. number of mutations per 1 million gametes
Types of Point Mutations
● Base-pair substitution mutation: a change from one base pair to another
○ Transition mutation: a mutation from one purine-pyrimidine base pair to the
other purine-pyrimidine base pair
■ e.g C → T + G → A
○ Transversion mutation: a mutation from a purine-pyrimidine base pair to a
pyrimidine-purine base pair
■ e.g. C → A + G → T
○ Missense mutation: a gene mutation in which a base-pair change causes a
change in an mRNA codon so that a
different amino acid is inserted into the
polypeptide
■ Phenotypic change can result →
depends on the amino acid
change involved
■ e.g. 5’-AAA-3’ → 5’-GAA-3’
1
, ● AAA=lysine, GAA=glutamic acid
○ Nonsense mutation: a gene mutation in which a base-pair change alters an
mRNA codon for an amino acid to a stop (nonsense) codon
■ Causes premature termination of polypeptide chain synthesis →
shorter-than-normal polypeptide fragments are released
■ e.g. 5’-AAA-3’ → 5’-TAA-3’
● AAA=lysine, UAA=stop codon
○ Neutral mutation: a base-pair change in a gene that changes a codon in the
mRNA such that the resulting amino acid substitution produces no detectable
change in the function of the protein translated from that message
■ Subset of missense mutations in which the new codon codes for a
different amino acid that is chemically equivalent to the original/the
amino acid is not functionally important
■ Does not affect the proteins function
■ e.g. 5’-AAA-3’ → 5’-AGA-3’
● AAA=lysine, AGA=arginine → similar properties
○ Silent mutation/synonymous mutation: a mutation the changes a base pair in
a gene, but the altered codon in the mRNA specifies the same amino acid in
the protein
■ Protein → wild-type function
■ e.g. 5’-AAA-3’ → 5’-AAG-3’
● AAA=lysine, AAG=lysine
● Frameshift mutation: if 1+ base pairs are added/deleted from a protein-coding gene,
the reading frame of an mRNA can change downstream of the mutation
● Classification of mutations
○ By cause
■ Spontaneous vs induced
○ By its effect on DNA
■ Point vs chromosomal
■ Substitution vs insertion/deletion
■ Transition vs transversion
○ By its effect on an encoded protein
■ Nonsense, missense, neutral, silent, frameshift
Spontaneous and Induced Mutations
● Mutagenesis: the creation of mutations
○ Spontaneous mutations: naturally occurring mutations
○ Induced mutations: Mutations that occur when an organism is exposed to a
physical or chemical agent → mutagen
Spontaneous Mutations
● Occur during DNA replication _ other stages of cell growth and division
● Can result from the movement of transposable genetic elements
● Mutation rate for individual genes → 10-4-10-6 per gene per generation
○ These rates and frequency values represent the mutations that become fixed
in DNA
● Most spontaneous mutations → corrected by cellular repair systems
2
, ○ Some remain uncorrected → permanent changes
DNA Replication Errors
● Base-pair substitution mutations: point mutations
involving a change from one base pair to another
○ Occur if mismatched base pairs form during
DNA replication
○ Chemically, each base can exist in alternative
states → tautomers
■ When a base changes state →
undergoes tautomeric shift
■ Keto form of each base → responsible
for the normal Watson-Crick base pairing
(AT and CG)
■ Non-Watson-Crick base paring can
result if a base is in a rare tautomeric
state → enol form
● Mismatch caused by a base shifting to a rare
tautomeric state → can result in a mutation
● Small additions and deletions can occur spontaneously
during replication
○ Occur because of displacement (looping out) of bases from the template or
the growing DNA strand
■ If DNA loops out of the template strand → DNA polymerase skips the
looped-out base(s) → produces a deletion mutation
■ If DNA polymerase synthesizes (an) untemplated base(s) → new DNA
loops out from the template → produces an addition mutation
Spontaneous Chemical Changes
● Depurination: the loss of a purine from the DNA when the bond hydrolyzes between
the base and the deoxyribose sugar → results in an apurinic site
● Deamination: the removal of an amino group from a base
○ e.g. deamination of cytosine → uracil
■ Repair system replaces most uracils in DNA
■ If uracil is not replaced → adenine will be incorporated in the new
DNA strand opposite it during replication
● CG-to-TA transition mutation
○ e.g. deamination of modified base 5-methylcytosine (5mC) → thymine
■ If it is not corrected → GC-to-AT transition mutation
■ Not likely to be corrected
■ Locations of 5mC on genome → often appear as mutational hot spots
● Depurination + deamination → repairable by base excision repair systems
Induced Mutations
● Mutations can be induced by exposure to physical/chemical mutagens
○ e.g. radiation
3
, Radiation
● UV light → causes mutations by increasing the chemical energy of certain molecules
in DNA
○ Formation of abnormal chemical bonds between adjacent pyrimidine
molecules in the same strand of the double helix
■ Induced mostly
between adjacent
thymines → forms
thymine dimers
■ Produces a bulge in
the DNA strand →
disrupts the normal
pairing of T bases with the corresponding A bases on the opposite
strand
■ Replication cannot proceed past the lesion → cell dies
● Ionizing radiation penetrates tissues → collides with molecules → knocks electrons
out of orbits → ions are created
○ Ions can result in the breakage of covalent bonds
■ e.g. sugar-phosphate backbone of DNA
○ Low levels → point mutations are produced
Chemical Mutagens
● Base analogs: bases that are similar to those normally found in DNA
○ Exist in normal and rare tautomeric
states
○ Pairs with a different normal base
in DNA
○ e.g. 5-bromouracil (5BU)
■ Has a bromine residue
instead of the methyl group
of thymine
■ Normal state → resembles
thymine
● Pairs with adenine
in DNA
■ rare tautomeric state →
resembles cytosine
● Pairs with guanine
in DNA
■ Induces mutations by
switching between its 2
chemical states once the
base analog has been incorporated into the DNA
● Base-modifying agents: chemicals that act as mutagens by modifying the chemical
structure and properties of bases
○ Deaminating agents
■ e.g. nitrous acid (HNO2)
4
Chapter 7 - DNA Mutation, DNA Repair, and
Transposable Elements
DNA Mutation
Mutations Defined
● Mutation: the process by which the sequence of base pairs in a DNA molecule are
altered
● Mutant cell: cell with a mutation
● Somatic mutation: when a mutation happens in a somatic cell
○ Affects the individual in which the mutation occurs
○ Not passed onto the succeeding generation
● Germ-line mutation: when a mutation happens in a reproductive cell (gamete)
○ Transmitted by the gametes to the next generation
○ Individual with the mutation in somatic + germ-line cells is produced
● Quantitative measure of occurance of mutations
○ Mutation rate: probability of a particular kind of mutation as a function of time
■ e.g. number of mutations per nucleotide pair per generation
■ e.g. number of mutations per gene per generation
○ Mutation frequency: number of occurances of a particular kind of mutation,
expressed as the proportion of cells/individuals in a population
■ e.g. number of mutations per 100.000 organisms
■ e.g. number of mutations per 1 million gametes
Types of Point Mutations
● Base-pair substitution mutation: a change from one base pair to another
○ Transition mutation: a mutation from one purine-pyrimidine base pair to the
other purine-pyrimidine base pair
■ e.g C → T + G → A
○ Transversion mutation: a mutation from a purine-pyrimidine base pair to a
pyrimidine-purine base pair
■ e.g. C → A + G → T
○ Missense mutation: a gene mutation in which a base-pair change causes a
change in an mRNA codon so that a
different amino acid is inserted into the
polypeptide
■ Phenotypic change can result →
depends on the amino acid
change involved
■ e.g. 5’-AAA-3’ → 5’-GAA-3’
1
, ● AAA=lysine, GAA=glutamic acid
○ Nonsense mutation: a gene mutation in which a base-pair change alters an
mRNA codon for an amino acid to a stop (nonsense) codon
■ Causes premature termination of polypeptide chain synthesis →
shorter-than-normal polypeptide fragments are released
■ e.g. 5’-AAA-3’ → 5’-TAA-3’
● AAA=lysine, UAA=stop codon
○ Neutral mutation: a base-pair change in a gene that changes a codon in the
mRNA such that the resulting amino acid substitution produces no detectable
change in the function of the protein translated from that message
■ Subset of missense mutations in which the new codon codes for a
different amino acid that is chemically equivalent to the original/the
amino acid is not functionally important
■ Does not affect the proteins function
■ e.g. 5’-AAA-3’ → 5’-AGA-3’
● AAA=lysine, AGA=arginine → similar properties
○ Silent mutation/synonymous mutation: a mutation the changes a base pair in
a gene, but the altered codon in the mRNA specifies the same amino acid in
the protein
■ Protein → wild-type function
■ e.g. 5’-AAA-3’ → 5’-AAG-3’
● AAA=lysine, AAG=lysine
● Frameshift mutation: if 1+ base pairs are added/deleted from a protein-coding gene,
the reading frame of an mRNA can change downstream of the mutation
● Classification of mutations
○ By cause
■ Spontaneous vs induced
○ By its effect on DNA
■ Point vs chromosomal
■ Substitution vs insertion/deletion
■ Transition vs transversion
○ By its effect on an encoded protein
■ Nonsense, missense, neutral, silent, frameshift
Spontaneous and Induced Mutations
● Mutagenesis: the creation of mutations
○ Spontaneous mutations: naturally occurring mutations
○ Induced mutations: Mutations that occur when an organism is exposed to a
physical or chemical agent → mutagen
Spontaneous Mutations
● Occur during DNA replication _ other stages of cell growth and division
● Can result from the movement of transposable genetic elements
● Mutation rate for individual genes → 10-4-10-6 per gene per generation
○ These rates and frequency values represent the mutations that become fixed
in DNA
● Most spontaneous mutations → corrected by cellular repair systems
2
, ○ Some remain uncorrected → permanent changes
DNA Replication Errors
● Base-pair substitution mutations: point mutations
involving a change from one base pair to another
○ Occur if mismatched base pairs form during
DNA replication
○ Chemically, each base can exist in alternative
states → tautomers
■ When a base changes state →
undergoes tautomeric shift
■ Keto form of each base → responsible
for the normal Watson-Crick base pairing
(AT and CG)
■ Non-Watson-Crick base paring can
result if a base is in a rare tautomeric
state → enol form
● Mismatch caused by a base shifting to a rare
tautomeric state → can result in a mutation
● Small additions and deletions can occur spontaneously
during replication
○ Occur because of displacement (looping out) of bases from the template or
the growing DNA strand
■ If DNA loops out of the template strand → DNA polymerase skips the
looped-out base(s) → produces a deletion mutation
■ If DNA polymerase synthesizes (an) untemplated base(s) → new DNA
loops out from the template → produces an addition mutation
Spontaneous Chemical Changes
● Depurination: the loss of a purine from the DNA when the bond hydrolyzes between
the base and the deoxyribose sugar → results in an apurinic site
● Deamination: the removal of an amino group from a base
○ e.g. deamination of cytosine → uracil
■ Repair system replaces most uracils in DNA
■ If uracil is not replaced → adenine will be incorporated in the new
DNA strand opposite it during replication
● CG-to-TA transition mutation
○ e.g. deamination of modified base 5-methylcytosine (5mC) → thymine
■ If it is not corrected → GC-to-AT transition mutation
■ Not likely to be corrected
■ Locations of 5mC on genome → often appear as mutational hot spots
● Depurination + deamination → repairable by base excision repair systems
Induced Mutations
● Mutations can be induced by exposure to physical/chemical mutagens
○ e.g. radiation
3
, Radiation
● UV light → causes mutations by increasing the chemical energy of certain molecules
in DNA
○ Formation of abnormal chemical bonds between adjacent pyrimidine
molecules in the same strand of the double helix
■ Induced mostly
between adjacent
thymines → forms
thymine dimers
■ Produces a bulge in
the DNA strand →
disrupts the normal
pairing of T bases with the corresponding A bases on the opposite
strand
■ Replication cannot proceed past the lesion → cell dies
● Ionizing radiation penetrates tissues → collides with molecules → knocks electrons
out of orbits → ions are created
○ Ions can result in the breakage of covalent bonds
■ e.g. sugar-phosphate backbone of DNA
○ Low levels → point mutations are produced
Chemical Mutagens
● Base analogs: bases that are similar to those normally found in DNA
○ Exist in normal and rare tautomeric
states
○ Pairs with a different normal base
in DNA
○ e.g. 5-bromouracil (5BU)
■ Has a bromine residue
instead of the methyl group
of thymine
■ Normal state → resembles
thymine
● Pairs with adenine
in DNA
■ rare tautomeric state →
resembles cytosine
● Pairs with guanine
in DNA
■ Induces mutations by
switching between its 2
chemical states once the
base analog has been incorporated into the DNA
● Base-modifying agents: chemicals that act as mutagens by modifying the chemical
structure and properties of bases
○ Deaminating agents
■ e.g. nitrous acid (HNO2)
4
