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Flashcards in Lecture 8 cards Deck (104):
1

Mutation

refers to a heritable change in genetic material

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What are the 3 main categories of mutations?

1. gene mutations, 2. chromosome mutations,3. genome mutations

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gene mutations

small change in DNA .. Affects a single or a few genes.

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chromosome structure

changes in chromosome structure

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genome mutations

changes in chromosome number

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Mutations provide for _________ ____________, a component that necessary for evolution to occur?

allelic variation

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Mutation Rate

likelihood that a gene will be altered by a new mutation; (# new mutations in a gene)/(cell generation)

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What factors can influence mutation rate?

-mutagens

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mutS

lack of this gene = no repair made

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What 2 gene characteristic factors can affect the rate of mutation?

1. size of gene (...larger genes have a greater chance for mutation);2. hot spots ( locations on chromosome that are more susceptible to mutation)

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Somatic hypermutation (SHM)

mechanism that involves a programmed process of mutation affecting the variable regions of immunoglobulin genes which diversifies B cell receptors to expand their recognition range

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Mutation Frequency

the number of mutant alleles divided by the total number of that allele in a population

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What is the mutation frequency if: 1 million bacteria were plated and 10 of them were mutant?`

1 in 100,000 or 10^-5

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What 3 things does mutation frequency depend on?

1- mutation rate; 2- timing of the mutation; 3- likelihood that the mutation will be passed on to future generations

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Different types of DNA mutations:

-point mutation,-INDEL; -silent mutations; -missense mutations; -nonsense mutations; -frameshift mutations

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point mutation

change in a single base pair

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What are the 2 types of point mutations?

1. transition; 2. transversions

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What is a Transition point mutation?

a change of a pyrimidine (C,T) to another pyrimidine (C,T) OR a purine (A,G) to another purine (A,G)

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What is a Transversion point mutation?

a change of a pyrimidine to a purine or vice versa

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Which is the more common type of point mutation?

Transition

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INDEL

*in*sertion or *del*etion of base pairs

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silent mutations

do not alter the amino acid sequence of the polypeptide ( due to degeneracy and wobble)

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missense mutation

base substitutions in which an amino acid change occurs

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nonsense mutations

base substitutions that change a normal codon to a stop codon

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frameshift mutations

the addition or deletion of bases not divisible by three

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Explain the effect of a nonsense mutation on translation

(figure slide #12) altered codon= a nonsense codon and therefore premature termination of translation

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Different types of gene mutations:

-forward mutation; -reverse mutation; -suppressor mutation

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forward mutation

changes the wild-type genotype into a new variation

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reverse mutation

changes a mutant allele back to the wild-type allele

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Mutations described based on their effects on the wild-type phenotype:

--deleterious mutations;--beneficial mutations;-- conditional mutations;--neutral mutations

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deleterious mutations

decrease the chances of survival

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beneficial mutations

enhance the survival or reproductive success of an organism

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conditional mutations

affect the phenotype only under a defined set of conditions.;-temperature-sensitive mutation

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supressor mutations

describes how mutations can be altered: a second mutation that counteracts the effects of a first mutation

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2 types of suppressor mutations:

1- intragenic suppressors; 2-intergenic suppressors

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*intra*genic suppressors

second site is within the same gene as the first mutation

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*inter*genic suppressors

second site is in a different gene from the first mutation; (figure on slide #15); -tRNA suppressor gene mechanism for nonsense mutation:

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The tRNA suppressor is an example of which type of suppressor mutation?

intergenic suppression

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What is the result of the tRNA suppressor gene mechanism for nonsense mutation?

transcription and translation of mRNA with nonsense codon. The altered codon = nonsense codon. The altered anticodon in mutant tRNA gene. There is no premature termination of translation so a complete polypeptide is formed with one incorrect amino acid !

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chromosomal breakpoint

occurrence of this within a gene is affected by chromosomal rearrangement

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position effect

a gene is left intact but the expression is altered bc of its new location

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What are 2 common reasons for position effects?

(figure on slide # 16);1-movement to a position next to regulatory sequences;2-movement to a heterochromatic region

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Germ-line mutations VS somatic cell mutations

can be passed to future generations.... cannot be passed to future generations

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Where can somatic cell mutations occur?

-all body cells (no gametes); -autosome or sex chromosome

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spontaneous mutations

-result from abnormalties in cellular/biological processes ; -underlying cause originates within the cell

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induced mutation

-caused by environmental agents

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mutagens

agents that can alter DNA structure (can be chemical or physical)

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Salvadore Luria and Max Delbruck: what did they study & what was their question?

-studied resistance of E. coli to infection by bacteriophage T1. ; -Is ton^r due to spontaneous mutations or to a physiological adaptation that occurs at a low rate?; -fluctuation test

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ton^r

T1 resistance

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Luria-Delbruck: What does the physiological adaptation theory predict?

the number of ton^r bacteria is an essentially constant proportion of the total population. (in different bacterial populations this proportion should be very similar)

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Luria-Delbruck: What does the random mutation theory predict?

the number of ton^r bacteria will fluctuate in different bacterial populations based upon the timing of the mutation

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fluctuation test

figure on slide #22

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Joshua and Ester Lederberg

looked at relationship bw mutations and environmental conditions that select for mutation.

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What were the two theories of the J&E Lederberg experiment?

1- physiological adaptation theory (Lamarck's viewpoint); 2- random mutation theory (Darwin's viewpoint)

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Describe the Joshua and Ester Lederberg experiment:

figure on slide #25

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CRISPR system

Lamarck wasn't entirely wrong .... well, at least for the bacteria that carry this system: adaptive immune defense

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3 chemical changes that lead to spontaneous mutations:

1- depurination; 2- deamination; 3- tautomeric shift

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spontaneous mutations can occur by mispairings or "_________" during DNA replication : all of these fall under this category

-wobble pairing; -INDELs; -"slipping"-slippage

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depurination

removal of a purine: Adenine or Guanine

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How does depurination occur?

covalent bond bw deoxyribose and purine base is somewhat unstable and it undergoes hydrolysis (beta-N-glycocidic link) that releases the base from the sugar.

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apurinic site

lack of a purine caused by depurination

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deamination

removal of an amino group from cytocine resulting in uracil!

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What happens if DNA repair enzymes do not recognize the faulty Uracil (from deamination)?

a C-G to A-T mutation will result during later rounds of DNA replication

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deamination of 5-methyl cytosine results in...

Thymine (T)

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What happens when the deamination of 5-methyl cytosine occurs?

DNA repairenzymes cannot determine which of the two bases on the DNA strands is the incorrect base

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methylated cytosine bases tend to create _____ _____ for mutation

hot spots (CpG islands)

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Tautomeric shift

a temporary change in base structure

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2 forms of bases:

1-the common (Keto or Amino); 2-the uncommon (Enol or Imino)

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How do the uncommon forms of bases created by taotomeric shifts differ from the common forms?

Alternate forms differ by a single proton shift in the molecule

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Stable form of Thymine and Guanine

Keto

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Stable form of Adenine and Cytosine

Amino

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T and G can interconvert to an ______ form

enol

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A and C can interconvert to an ______ form

Imino

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Rare forms of bases can promote....

incorrect AC and GT base pairs

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When must a tautomeric shift occur in order for it to cause a mutation?

just prior to DNA replication, when the DNA is not in double helix

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Example of slippage

figure on slide # 36

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DNA loops out on template strand

PolIII skips bases

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DNA loops out on daughter strand

PolIII adds random bases

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Why might slippage occur?

long run of same nucleotide

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Slipped Strand Mispairing:

if a DNA strand loops out and becomes displaced or if a DNA polymerase slips small insertions and deletions can occur

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Where is replication slippage common?

particularly poly-G tracts

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trinucleotide repeat expansion (TNRE)

causes several genetic diseases... in people with these disorders the length of a trinucleotide repeat has increased above a certain critical size and then disease symptoms occur

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If expansion due to TNRE occurs within the coding sequence of the gene....

proteins aggregate with each other. typically the expansion is a CAG codon for glutamine)

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If the expansion due to TNRE is located in noncoding regions of genes expansions may:

-cause abnormal changes in RNA structure

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2 unusual features in common within TNRE disorders:

1-Anticipation ; 2-anticipation usually depends on who the disease is inherited from

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anticipation

the severity of the disease (a TNRE disorder) tends to worsen in future generations

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chemical mutagens are categorized as:

-base analogs; -base modifiers; -intercalating agents

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base analogs

(may change pairing) become incorporated into daughter strands during DNA replication

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base modifiers

(change one base into another) covalently modify the structure of a nucleotide

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base modifier examples:

nitrous acid : replaces amino groups with keto groups ; nirogen mustards and ethyl methanesulfonate (EMS)

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intercalating agents

(alter the shape of DNA and cause INDEL) contain flat planar structures that intercalate themselves into DNA... when inserted, this distorts the helical structure)

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what happens when DNA containing intercalating agents are replicated?

the daughter strand may contain single-nucleotide additions and/or deletions resulting in frameshifts

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intercalating agents examples

acridine dyes; proflavin;Ethidium Bromide

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2 types of physical mutagens:

1- ionizing radiation; 2- nonionizing radiation

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ionizing radiation

short wavelength and high frequency

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free radicals can be created by

ionizing radiation

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ionizing radiation can cause:

-base deletions; -oxidized bases; -single nicks in DNA strands;-cross-linking; -chromosomal breaks

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nonionizing radiation

lower energy than ionizing (includes UV light)

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nonionizing radiation causes:

the formation of cross-linked pyrimidine dimers (C or T) called *cyclobutane pyrimidine dimer* or less common 6,4-photoproducts

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when might pyrimidin dimers cause mutations?

when DNA is replicated

101

What is the purpose of an Ames test?

to determine if something is a mutagen

102

Ames test

uses a strain of Salmonella typhimurium that cannot synthesize histidine (amino acid) [it has a point mutation (or a deletion) in a gene involved in histidine biosynthesis]. A second mutation (reversion) may occur restoring ability to synthesize histidine. *Ames test monitors the rate at which the second mutation occurs*

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The restoration of the ability to synthesize histidine in the S. typhimurium strain used in an Ames test is.....

a Reversion (reverse mutation) --> second mutation

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Describe an Ames test

figure on slide #52