Lecture 17 Flashcards
(65 cards)
1
Q
mutations
A
an inherited change in genetic information
2
Q
somatic mutations
A
arise in somatic tissues (which do not produce gametes). the mutation is passed on to daughter cells, leading to a population of genetically identical cells (a clone)
3
Q
germ-line mutations
A
arise in cells that ultimately produce gametes. A germ-line mutation can be passed to future generations, producing individuals that carry the mutation in their somatic and germ-line cells.
4
Q
chromosomal mutations
A
large-scale alterations that affect chromosome structure or number
5
Q
gene mutations
A
a relatively small lesion that affects a single gene
6
Q
base substitution
A
the alteration of a single-nucleotide in the DNA
7
Q
transition
A
a purine is replaced by a different purine, or a pyrimidine is replaced by another pyrimidine
8
Q
transversion
A
a purine replaced by a pyrimidine or a pyrimidine replaced by a purine
9
Q
insertions and deletions (indels)
A
the addition or deletion of one or more nucleotide pairs in the DNA
10
Q
frameshift mutations
A
deletions or insertions within protein encoding sequences may cause a frame shift and thus alter all amino acids encoded by nucleotides following the mutation
11
Q
in-frame mutations
A
insertions or deletions of THREE nucleotides will leave the reading frame intact, but add or delete an amino acid in the protein product
12
Q
expanding nucleotide repeats
A
mutations in which the number of copies of a set of nucleotides increases in number
13
Q
Huntington’s disease
A
CAG expanding repeats found inside a coding region
14
Q
forward mutation
A
alters the wild-type phenotype
15
Q
reverse mutation
A
changes a mutant phenotype into the wild type
16
Q
missense mutation
A
a base substitution that results in a different amino acid in the protein
17
Q
nonsense mutation
A
changes a sense codon into a termination codon
18
Q
silent mutation
A
changes a codon to synonymous codon that specifies the same amino acid
19
Q
neutral mutation
A
- a missense mutation that alters the amino acid sequence of the protein, but does not change its function
- occur when one amino acid is replaced by another that is chemically similar or when the affected amino acid has little influence on protein function
20
Q
loss-of-function mutations
A
cause the complete or partial absence of normal protein function
21
Q
gain-of-function mutation
A
- produces an entirely new triat, or it causes a trait to appear in an inappropriate tissue or inappropriate time in development
- frequently dominant in their expression
22
Q
conditional mutation
A
- expressed only under certain conditions
- i.e. elevated temperatures
23
Q
lethal mutation
A
causes premature death
24
Q
suppressor mutation
A
- hides or suppresses the effect of another mutation
- occurs at a site that is distinct from from the site of the original mutation
- two classes inorganic and intergenic
25
reverse mutation
the mutated site changes back to the original wild-type sequence
26
intragenic suppressor mutation
in the same gene as that containing the mutation being suppressed
27
ways intragenic suppressor mutations work
- by changing a second nucleotide in the same codon altered by the original mutation, producing a codon that specifies the same amino acid as that specified by the original unmutated codon
- by suppressing a frameshift mutation to restore the former reading frame.
- by making compensatory changes in the protein. A first missense mutation may alter the folding of the polypeptide chain by changing the way in which the amino acids in the protein interact. A second missense mutation at a different site (the suppressor) may recreate the original folding pattern by restoring interactions between the amino acids.
28
intergenic suppressor mutation
occurs in a different gene than that containing the mutation being suppressed
29
mutation rate
- the frequency with which a wild-type allele at a locus changes into a mutant allele
- generally expressed as the number of mutations per biological unit, which may be mutations per cell division, per gamete, or per round of replication
30
factors affecting mutation rates
- frequency with which a change takes place in the DNA. Changes in DNA can arise spontaneously or can be induced by chemical, biological or physical agents in the environment
- probability that a mutation will be repaired
- probability that a mutation will be detected. Usually detected by their phenotypical effects. Some may appear to arise at a higher rate because they are easier to detect
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spontaneous mutations
occur under natural conditions
32
induced mutations
result from changes caused by environmental chemicals or radiation
33
tautomeric shifts
- purine and pyrimidine bases exist in different chemical forms called tautomers in which the positions of the protons change
- the two tautomeric forms of each base are in dynamic equilibrium although one form is more common
- standard Watson-Crick base pairs are between the common forms of the bases, but if the bases are in rare tautomeric forms, other base pairings are possible
34
mispairings due to other stuctures
- mispairings may also occur through wobble, in which normal, protenated and other forms are able to pair because of flexibility in the DNA
- thymine-guanine wobble
- cytosine-adenine protonated wobble
35
incorporation eror
- the incorporation of a mismatched base into a nucleotide chain
- the original incorporated error leads to a replication error which creates a permanent mutation, because all the base pairings are correct and there is no mechanism for the repair system to detect the error
36
strand slippage
- occurs when one nucleotide strand forms a small loop in replication
- if the looped out nucleotides are on the newly synthesized strand, an insertion results
- if the looped out nucleotides are on the template strand, then the newly replicated strand has a deletion
37
unequal crossing over
- can result from misalignment which is most common in regions of repeated sequences or homopolymeric repeats. - can cause insertions and deletions
- can produce duplicated copies of sequences, which promote further unequal strand slippage. may explain expanding nucleotide repeats
38
depurination
- the loss of a purine base from a nucleotide
- results when the covalent bond connecting the base to the sugar breaks, creating an apurinic site
- apurinic site cannot serve as a template for base pairing so in incorrect nucleotide (usually adenine) incorporated opposite the site
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deamination
- the loss of an amino group from a base
| - can alter the pairing properties of a base (deamination of cytosine produces uracil)
40
mutagen
any environmental agent that increases the rate of mutation above the spontaneous rate
41
base analog
- chemical mutagens with structural similar to any of the four standards bases in DNA
- if present, will be incorporated into DNA since DNA pol cannot distinguish them from standard bases
42
other types of damage
done by alkaylating agents, deamination, hydroxyl amine, and oxidative reactions
43
intercalating agents
- produce mutations by sandwiching themselves (intercalating) between adjacent bases in DNA, distorting the 3D structure of the helix and causing single-nucleotide insertions and deletions in replication
- frequently cause frameshift mutations
44
ionizing radiation
- x-rays, gamma rays, and cosmic rays
- dislodge electrons from the atoms that they encounter, changing stable molecules into free radicals and reactive ions, which then alter structures of bases and break phosphodiester bonds in DNA
- also results in double-strand break in DNA and can produce chromosome mutations
45
UV light
- less energy than ionizing radiation and does not eject electrons but still mutagenic
- purine and pyrimidine bases absorb UV light, resulting in formation of chemical bonds between adjacent pyrimidines on the same strand of DNA, creating pyrimidine dimers
46
pyrimidine dimers
block replication and transcription
47
Ames test
- mutagenesis in bacteria can serve as an indicator of mutagenesis in humans (detects frameshift or base substitution mutations)
- uses different auxotrophic strains of S. typhimurium that have defects in LPS
- DNA repair system inactivated, enhancing susceptibility to mutagens
- each strain carries a his- mutation and the bacteria are plated on a medium that lacks histidine. only bacteria that have undergone a reverse mutation of the histidine gene can synthesize amino acid and grow
- compound first incubated in mammalian liver extract that contains metabolic enzymes
- different dilutions of a chemical to be tested are incubated with bacteria and liver extract then plated to see if more grow
- any chemical that significantly increases the number of colonies derived from the chemical-treated sample is considered to be mutagenic
48
transposable elements
- sequences that can move in a genome
- found in the genomes of all organisms and most are able to insert at many locations.
- their movement causes mutation, either by inserting into a gene and disrupting it, or by causing DNA rearrangements such as deletions, duplications, and inversions
49
flanking direct repeats
- from 3-12 bp long present in the genome on both sides of most transposable elements
- transposable elements insert itself into DNA
- replication of single stranded DNA creates franking direct repeats
50
terminal inverted repeats
- recognized by the enzymes that catalyze transposition and are requirement for movement to take place
51
transposase
used to make the staggered cut in the DNA and to integrate the transposable element into the new site
52
DNA transposons
transposable elements that transpose as DNA elements
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retrotransposons
transposable elements that move through an RNA intermediate
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reverse transcriptase
copies DNA into RNA then back into DNA
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How organisms limit the amount of transposition that occurs
- methylating DNA or alternating chromatin structure in the regions where transposons are common
- DNA methylation usually suppresses transcription preventing production of the transposase enzyme
56
types of DNA repair
- mismatch
- direct
- base excision
- nucleotide excusion
- homologous recombination
- nonhomologous recombination and joining
57
mismatch repair
- correct many incorrectly inserted nucleotides that escape proofreading
- enzyme complex excises segment containing incorrectly paired nucleotides from newly synthesized strand and uses original strand as template to replace them.
ADDITIONAL INFO
- repair complex with unmethylated GATC sequence in close proximity to the mismatched bases
- nicks the methylated strand at the GATC site and degrades the strand between the nick and the mismatched bases
- DNA polymerase and DNA ligase fill in the gap on the unmethylated strand with correctly paired nucleotides
58
direct repair
- repair pyrimidine dimers
| - nucleotides are not replaced but are converted back into their original (correct) structures
59
photolyase
correct pyrimidine dimers by using light energy to break the covalent bonds between the dimers
60
base excision repair
repairs abnormal bases, modified bases, and pyrimidine dimers
- DNA glycolyase first excises modified base then entire nucleotide replaced.
ADDITIONAL INFO
- excision of modified bases catalyzed by DNA glycolyases, recognize and removes a specific type of modified base by cleaving the bond that links it to the 1' carbon atom of the sugar
- after base removed, AP endonuclease cuts the phosphodiester bond and other enzymes remove the sugar
- DNA pol then adds one or more new nucleotides to the 3' OH and the nick in the backbone is sealed by DNA ligase
61
nucleotide excision repair
- the removal of bulky DNA lesions like pyrimidine dimers that distort the helix
- corrects bulky DNA lesions by separating the two nucleotide strands at the damaged region, part of the damage strand is cleaved on both sides of the damage, and the gap left is filled by DNA polymerase and sealed by DNA ligase.
62
homologous recombination
- repairs are made by using the identical or nearly identical information in another DNA molecule, usually sister chromatid. DNA repair through homologous recombination uses the same mechanism employed in the process of homologous recombination that is responsible for crossing over
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nonhomologous end joining
- double stranded breaks are prepared without using homologous template.
- proteins recognize the broken ends of the DNA, bind to the ends, and join them together
- more error prone process than homologous recombination and may lead to deletions, insertions and translocations
64
fragile x syndrome
- expanding nucleotide repeats
- the tip of each long arm of X chromosome is attached by only a slender thread
- multiple copies of CGG
65
synonymous codon
code for the same amino acid
