Summary GP (Genome to Population) Self-study (Part 2/2)
13 views 0 purchase
Course
Van genoom tot populatie
Institution
Universiteit Utrecht (UU)
Book
iGenetics: Pearson International Edition
This is a summary of all Russell's self-study material and the additional material from seminar 19 for the course GP (Genome to Population), of the veterinary medicine study.
Gene expression and post-transcriptional modification
All for this textbook (12)
Written for
Universiteit Utrecht (UU)
Diergeneeskunde
Van genoom tot populatie
All documents for this subject (39)
Seller
Follow
ankejesse
Reviews received
Content preview
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
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller ankejesse. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $4.27. You're not tied to anything after your purchase.
