Genetics ch 19: Gene mutation and DNA Repair

mutation

a heritable change in the genetic material

• •Provide allelic variations

• •Are the foundation for evolutionary change

• •Can be detrimental if they result in an allele that functions more poorly than the original

Mutations…

• •Provide_______

• •Are the foundation for______

• •Can be detrimental if…

true!

T/F: Mutations can occur at the chromosomal or gene level

false: usually affect one gene

T/F: gene mutations usually affect several genes

a point mutation is a change in a single base pair and involves a base substitution

a _______ is a change in a single base pair and involves a _______

A transition is a change of a pyrimidine (C, T)  to another pyrimidine or a purine (A, G) to another purine

A ______ is a change of a pyrimidine (C, T)  to another pyrimidine or a purine (A, G) to another purine

• A transversion is a change of a pyrimidine to a purine or vice versa

• A _____ is a change of a pyrimidine to a purine or vice versa

false! transtitions are more common than transversions

T/F: transversions are more common than transitions

silent mutation, missense, and nonsense

a base substitution can cause … 1, 2, 3 (types of mutations)

a frameshift

addition and deletion of short DNA sequences causes…

inhibitory (missense neutral or inhibitory)

a frameshift, nonsense, and sometimes a missense mutation have what effect on protein function?

silent

a ___ mutation has no effect on protein function

missense

sickle cell anemia is an example of a ____ mutation becuase eone amino acid substutuion changes blood cell morphology

false!

T/F: gene mutations occuring outside of a coding sequence cannot influence gene expression

promoter

a mutation in the ___ sequence may increase or decrease the rate of transcription

Regulatory element/operator site

a mutation in the ___ sequence may disrupt the ability of the gene to be properly regulated

5′-UTR/3′-UTR

a mutation in the __ sequence May alter the ability of mRNA to be

translated; may alter mRNA stability

Splice recognition sequence

a mutation in the ___ sequence May alter the ability of pre-mRNA to be properly spliced

reverse mutation or reversion

a _____ mutation or ___ changes a mutant allele back tot he wild-type

neutral

a ___ mutation does not alter protein function

deleterious mutation / lethal mutation

a ____ mutation lowers the chance of survival and reproduction; extreme ones are called __ and result in death of organism

beneficial

a ___ mutation enhances the survival or reproductive success

true!

• Example: Sickle cell allele

  • •Heterozygotes have increased survival in the presence of malaria

T/F: whether a mutation is beneficial or deleterious can depend on environmental conditions

conditional

• •Example: Temperature-sensitive (ts) mutants 

• •Used by geneticists to study gene function

  • •Ex: E. coli with a ts mutation may grow in the range 33-38°C but not in the range 40-42°C

• A ______ mutation is one that affects the phenotype only under specific conditions

Suppressor

a second mutation that affects the phenotypic expression of a first mutation

suppression occurs in a second site

how is a suppressor different than a reversion?

Intragenic suppressor

– The second mutation is in the same gene as the first

Intergenic suppressor

The second mutation is in a different gene than the first

false! they have effects on both

T/F: intergenic suppressors may have effects on protein-protein interactions between 2 different proteins but not on subunits within the same protein coded by different genes

intergenic suppressor

this suppressor mutation usually involves a change in the expression of one gene that compensates for a loss-of-function mutation affecting another gene

Position effect

when a gene is relocated along a chromosome in a way that alters its gene expression

1. Movement to a position near regulatory sequences for a different gene

2. Movement to a heterochromatic region

There are two common reasons for position effects:

1. Movement to a position near _________

2. Movement to a ______ region

position effects due to movement of a gene to a position near regulatory sequences for a different gene

what is this?

position effects due to translocation to a heterochromatic chromosome

what is this?

Germ-line mutations

_______ are those that occur directly in a sperm or egg cell, or in one of their precursor cells

Somatic mutations

_______ occur in somatic cells at early or late stages of development

timing in development

Size of the affected region depends on the ______ of the somatic mutation

genetic mosaic

An individual with somatic cells that are genotypically different from each other is called a _______

false! this is true for germ-line mutations

T/F a trait due to somatic mutation is passed from parent to offspring

spontaneous mutation

a change in DNA structure that results from random abnormalities in biological or chemical processes

induced mutation

a mutation caused by environmental agents

induced

chemical substances, UV light, and X-rays changing DNA structure are examples of ___ mutations

Aberrant segregation

this spontaneous mutation may cause aneuploidy or polyploidy

Aberrant recombination

Spontaneous mutation described as abnormal crossing over which may cause deletions, duplications, translocations, and inversions

spontaneous

errors in DNA replication like A mistake by DNA polymerase may cause a point mutation which is a ___ mutation

spontaneous

transposable elements can insert themselves into the sequence of a gene and cause a ___ mutation

Depurination

•Removal of (guanine or adenine) from the DNA On rare occasions, the linkage between a purine (i.e., adenine or guanine) and deoxyribose can spontaneously break. If not repaired, this can lead to mutation.

Deamination

Removal of an amino group from the cytosine base; produces uracil Spontaneous changes in base structure can cause mutations if they occur immediately prior to DNA replication.

Tautomeric shifts

Spontaneous mutation described as the products of normal metabolic processes, such as reactive oxygen species, may be chemically reactive agents that can (temporarily) alter the structure of DNA.

 

• •Depurination

• •Deamination

• •Tautomeric shift

• Spontaneous mutations can arise by three types of chemical changes: 

1. .

2. .

3. .

depurination

______ is the most common type of chemical change

apurinic site

if a guanine is removed from a DNA strand what is the name of where the guanine once was?

• there is no complementary base present to specify the base

if an apurinic site is not repaired, a mutation may result becuase…

75% because 3 out of 4 nucleotides that may be added to the newly made strand opposite the apurinic site are no the correct one

when DNA that has an apurinic site is replicated, what is the probability that a mutation will occur?

deamination

what is it called when C—NH2 becomes C==O so cytosine becomes uracil?

• cytosine —> uracil (DNA repair enzymes recognize it as not belonging in DNA)

• 5-methyl cytosine —> thymine (repair enzymes can’t recognize thymine as not belonging bc its a DNA bp)

  • For this reason, methylated cytosine bases tend to create hot spots for mutation

deamination of cytosine produces ___ and deamination of 5-methyl cytosine produces ___. What makes this different?

keto form —> enol form

• The common, stable form of thymine and guanine is the _____ form

  • •At a low rate, T and G can interconvert to an ______ form

amino form —> imino form

Amino = Adenine (and cytosine is alphabetically closest)

• The common, stable form of adenine and cytosine is the _____

  • •At a low rate, A and C can interconvert to an ______

• •These rare forms promote AC and GT base pairs

immediately prior to DNA replication

To cause a mutation tautomeric shifts must occur…

oxygen

• Aerobic organisms use _____ as terminal acceptor in their electron transport chains

Reactive oxygen species (ROS)

molecules generated by normal metabolism, immune responses; Can damage cellular molecules

• Oxidative stress is an imbalance between synthesis and destruction of ROS

_______ is an imbalance between synthesis and destruction of ROS

oxidative DNA damage

ROS can cause changes in the DNA structure - called _______

False! eukaryotes and prokaryotes

T/F: methylation of cytosine occurs in only eukaryotes

guanine —-[O]—> 8-oxoguanine (8-oxoG)

___- bases are particularly vulnerable to oxidation which leads to many oxidation products like _____

8oxo-G base-pairs with adenine (instead of cytosine) which causes mutations in which a G-C base pair becomes a T-A base pair aka a transversion mutation

what does 8-oxoG do that is harmful?

False: increase!

T/F Trinucleotide sequences decrease from one generation to the next

trinucleotide repeat expansion (TNRE)

spinal and bulbar muscular atrophy (SBMA), Huntington disease (HD), Fragile X syndrome (FRAXA), spinocerebellar ataxia (SCA1), and myotonic muscular dystrophy are all examples of diseases that arise from ________

trinucleotide repeat expansion (TNRE)

The phenomenon/mutation in which a repeated sequence of 3 nucleotides can readily increase in number from one generation to the next

True

T/F: TRNE’s can occur in non-coding and coding sequences

CAG (glutamine)

Expansion may be within the coding sequence of the gene typically, ____ repeats which code for ____

• •Causes the proteins to aggregate with each other

• •Aggregation correlated with disease progression

when the are TNRE in coded regions and long tracks of glutamine are in the encoded protein….

anticipation

when the severity of the (TNRE) disease tends to worsen in future generations (doesn’t happen freuquently with TNRE disorders)

• Huntington disease, —> father

• myotonic muscular —> mother

• •In ______ anticipation is more likely to occur if inherited from the father

• •In _______, anticipation is more likely to occur if inherited from the mother

• a hairpin (or stem-loop) —> Leading to errors in DNA replication

• A key aspect of TNRE is that the triplet repeat can form ____ which leads to …

• abnormal changes in RNA structure which may produce methylated CpG islands to silence the gene

• Expansions located in noncoding regions are hypothesized to cause _______ which may produce …

mutagens

•An enormous array of agents can act as _____ to permanently alter the structure of DNA

mutagens

______ are often involved in the development of human cancers and are usually classified as chemical or physical

nitrous acid

____ deaminates bases (replaces amino groups with keto groups)

nitrogen mustard and ethyl methanesulfate

alkylating agents (2)

proflavine

intercalates within DNA helix (example of intercalating agent)

2-bromouracil and 2-aminopurine

base analogs (2)

x-rays

this physical mutagen causes base deletions, single-strand breaks in the DNA backbone, crosslinking, and chromosomal breaks

UV light

this physical mutagen Promotes formation of pyrimidine dimers, such

as thymine dimers

1. Base modifiers (alkylating agens)

2. Intercalating agents

3. Base analogs

3 types of chemical mutagens

deamination (base modification)

whats going on here?

base modification

deamination and alkylation are all examples of _____

These modified bases do not pair with the appropriate nucleotides in the daughter strand during DNA replication

what happens when nitrous acid change scytosine to uracil and adenine to hypoxanthine

alkylation (base modification)

nitrogen mustard and ethyl methanesulfonate (EMS) are involved in ____

Methyl or ethyl groups are covalently attached to the bases and disrupt the appropriate pairing between nucleotides

what happens during alkylation?

Intercalating agents

_______contain flat planar structures that insert themselves into the double helix and distorts helical structure

contain single-nucleotide additions and/or deletions resulting in frameshifts

When DNA containing intercalating agents is replicated, the daughter strands may ….

DNA replication

•Base analogs become incorporated into daughter strands during…

thymine

5-bromouracil is a _____ analogue (It can be incorporated into DNA instead of ___)

5BU undergoes a tautomeric shift and base pairs with G; When this occurs during DNA replication, TA base pair is changed to a 5BU-G base pair (base analog)

when 5-bromouracil incorporated into DNA instead of thymine, what happens?

x-rays and gamma rays —> makes free radicals

Ionizing radiation includes radiation from … and can create …

false! it cannot, only ionizing radiation penetrates deeply

T/F non-ionizing radiation can penetrate deeply into biological molecules material

• •Single-strand and double-strand breaks in DNA backbone

• •Cross-linking

• Oxidized bases

• •Base deletions

SCOB

ionizing radiation can cause … (4 things)

UV light

non-ionizing radiation includes _____

cross-linked thymine dimers cause mutations when that DNA strand is replicated

UV light/non-Ionizing radiation causes formation of … which cause…