1
Q
What are chromosome variations typically?
A
Permanent chromosomal
changes.
2
Q
When are chromosome variations passed to offspring?
A
Can be passed on to offspring if they occur in cells that will
become gametes (‘germline’
cells)
3
Q
What are the two types of chromosome variations?
A
- Chromosome rearrangement
- Variation in chromosome numbers
4
Q
What is chromosome rearrangement?
A
Chromosome rearrangement:
changes in the structure of
individual chromosomes.
5
Q
What is variation in chromosome numbers?
A
Variation in chromosome
numbers: changes in the
number of chromosomes. One
or more individual
chromosomes are added or
deleted.
6
Q
What are the 4 types of chromosomal rearrangements?
A
- Deletions
- Duplications
- Inversions
- Translocation
7
Q
What is a deletion?
A
Loss of a segment, either internal or terminal, from a chromosome.
8
Q
What are the two ways that deletions can arise?
A
Arise by terminal–ends breaking off (one break) or internal breaking and rejoining of incorrect ends (two breaks).
* OR – Arise by unequal crossing over.
9
Q
What is the major effect of deletions?
A
Major effect: loss of genetic
information (importance depends on what, and how much is lost).
10
Q
How do we detect deletions?
A
Deletion loops can be detected during meiosis
* we see a clear bulge in the one side of the chromosome that accommodates for the extra length of one leg.
11
Q
What are two other mechanisms by which we can detect deletions?
A
Also by a variety of molecular methods that detect lower heterozygosity or gene dosage
12
Q
What is the consequence of deletions for DNA?
A
A major consequence of deletions is the loss of DNA sequences
13
Q
What do phenotypic effects of deletions depend on?
A
Phenotypic effects depend on the size and location of deleted sequences.
14
Q
What do deletions spanning a centromere cause?
A
Deletions that span a centromere result in an acentric chromosome that will most likely be lost during cell division, may be lethal.
- cannot participate in cell division without centromere.
15
Q
How do deletions allow pseudodominance?
A
Deletions can allow expression of alleles that are normally recessive. Called pseudodominance.
- means that if the only copy in the heterozygote that is active is a recessive allele, we will think that it is dominant
16
Q
What else do deletions affect?
A
Deletions can affect gene dosage
17
Q
What happens when a gene is expressed of the gene dosage is altered?
A
Deletions can affect gene dosage.
o When a gene is expressed, the functional protein is normally produced at the
correct level or dosage.
18
Q
What is haploinsufficiency? When does this happen?
A
Some (not all) genes require two copies for normal of protein production; if
one copy is deleted a mutant phenotype can result called haploinsufficiency.
19
Q
Why does chromosome variation matter?
A
It plays a role in genetic disorders
20
Q
What is Cri du Chat?
A
This is a genetic disorder that is the result of having a shortened chromosome #5. Having just one of these being altered is enough to cause the distinct phenotype in this genetic disorder.
21
Q
What are duplications? What is tandem duplication?
A
Repetition of a chromosome segment.
* Tandem duplication is the simplest form (Ex. EF -> EFEF)
22
Q
What is the most common cause of duplications?
A
The most common cause of duplications is crossing over.
23
Q
How many genes can be duplicated?
A
Single gene or cluster of genes can be duplicated
24
Q
What is the typical effect of duplications on phenotype and viability?
A
Nothing has been lost, so duplications (especially smaller ones) often have little or no
effect on phenotype/viability.
- Offspring with duplications usually viable.
25
When does duplication cause problems?
But, some cases, excess or unbalanced ‘dosage’ of gene products (proteins) resulting
from duplications can cause problems.
- less of a problem than gene dosage
26
What is the most important role of duplications?
Very important in evolution, because extra copies of genes provide raw material for new
genes and adaptations.
27
How much of the genome is duplicated?
About 5% of human genome consists of duplications.
28
What is the origin of duplications?
Unequal crossing over of misaligned chromosomes during meiosis generates duplications (and deletions)
- deletions are not as important with this mechanism
29
How can we detect duplications?
Also by various molecular methods that detect higher gene dosage
- they can detect the loop/bulge of the extra DNA
30
What happens if both copies remain the same in duplication?
Both copies remain the same
*Redundancy (copy is a spare)
*Alter gene dosage, could have effect (likely no immediate effect)
31
What happens if one copy becomes inactive after duplication?
One copy becomes inactive
*Pseudogene
* typically a mutation that causes a premature stop codon
32
What happens when one copy gets a new function in duplication?
One copy acquires a new
function and evolves for new functions that increase fitness of the organism.
(Neofunctionalization)
Gene families
33
What is neofunctionalization?
Source of new genes, creating multigene families
34
Example of neofunctionalization?
The global gene family
- myoglobin gene
- alpha and beta gene clusters, which make up hemoglobin
- gamma globin in infants
35
Duplication effect on gene dosage?
Gene dosage may affect
phenotype.
* Amount of protein
synthesized is often
proportional to the number
of gene copies present, so
extra genes can lead to excess
proteins.
36
Example of gene dosage affecting genotype?
E.g., Bar region in Drosophila
(X chromosome). More
copies = fewer eye facets.
37
How many amylase gene copies do we have and what does it do?
Humans have 5-8 salivary amylase gene copies resulting from gene duplication
* Salivary amylase begins breakdown of starch to sugar in mouth
38
Which species has experienced duplications of genes active in its mouth that
parallel gene duplications that have occurred in humans?
Dogs, mice and pigs have similar amounts of duplications to humans, because they typically eat foods similar to what we eat.
39
What produces inversion?
Two breaks on a chromosome followed by reinsertion in the opposite orientation can produce an inversion.
40
What are the two types of insertion?
1. pericentric
2. paracentric
41
What is pericentric inversion?
This is when it occurs around the centromere (including the centromere)
42
What is a paracentric inversion?
This is when it occurs on one side of the centromere.
43
What are the typical effect of inversions on phenotype?
Often, none!
* However, sometimes there is an effect on phenotype, driven by the change in position of the gene(s)
* the effect is no change in dosage
44
What are the position effects?
This is a consequence of inversion.
- Change in position can alter expression, e.g. variegation in
Drosophila.
45
What happens to genes in/near chromatin due to position effects?
Genes in/near chromatin may not be expressed.
46
What is the major consequence of inversion for the production of gametes?
Inversion causes the suppression of recombination
47
What happens if no crossing over occurs in inversion?
If no crossing over occurs, gametes produced are usually viable because genetic
information is not lost or gained.
48
What happens if crossing over occurs in inversion?
If crossing over occurs......
...outside of inverted region - viable gametes.
...within inverted region - some nonviable gametes and reduced recombination frequency.
49
What happens with crossing over within a paracentric inversion?
Crossing over requires the formation of a loop, the formation of a dicentric chromatid and the loss of an acentric chromatid.
- we will see two that have the parent genotypes and two that are not viable.
50
What is a dicentric chromatid?
Dicentric refers to the bridge between two chromatids that the same chromatid are attached to
- it breaks as the two centromeres are pulled apart.
51
How does crossing over occur in pericentric inversion?
There is formation of a loop, and the recombinants will be nonviable, where we will again have 2 that resemble the parental types.
52
What is translocation?
Exchange of segments between nonhomologous chromosomes, or to a different region on same chromosome.
53
What are the two types of translocation?
Translocations between
chromosomes can be reciprocal/balanced (two-way) or non-reciprocal/non-balanced (one-way)
54
What happens if no genetic material is lost?
If no genetic material is lost,
considered a balanced
translocation.
55
What do translocations change?
As with inversions, translocations change the position of genes.
56
What does translocation alter and how?
This can alter expression of gene(s) because of association with different proteins, or formation of new gene
products (fusion proteins).
57
What are Philadelphia chromosomes?
* Fused BCR-ABL gene
* 5' section of BCR fused with most of ABL.
* Protein produce is a fusion that functions improperly – causes chronic myelogenous leukemia (CML), a rare form of cancer that affects certain types of white blood cells
58
What makes inversions particularly interesting?
Inversions are super interesting because they suppress recombination
59
What applications in evolution does inversion have?
Very interesting consequences
for adaptation and evolution!
* Lack of recombination within
inversions means that genes
within the inversions are free to diverge to produce different
adaptations
60
What is a ruff?
A European wading sandpiper
- has 3 types of males
61
Independent Ruff?
‘Independent’ males display in leks to attract females.
62
Faeder Ruff?
‘Faeder’ males mimic females, sneak copulations
63
Satellite Ruff?
‘Satellite’ males look like a somewhat drabber version of Independent males.
64
What is common between Faeder and Satellite males?
Faeder and satellite males have a 4.5Mb chromosomal inversion that arose 3.8 million years ago.
65
Which type of male came first?
Faeders came first. Later (ca 500k yr BP) a very rare crossover event restored some of the ‘independent’ version of the chromosome to the ‘faeder’ version, creating the ‘satellite’ version.
* The inversion is lethal in the
homozygous condition!!
66
How long has the inversion in Ruffs persisted?
Inversion has persisted for 3.8 Million Years because being a ‘Faeder’ is a successful
reproductive strategy, despite the ‘cost’ of fertilizations that are homozygous for the
inversion, and therefore not viable.
67
What is the mutation in humans that conveys fitness?
Comparable (in effect) to mutation that produces sickle cell anemia in humans...beneficial effects of being heterozygous outweigh the cost of producing
some offspring that are homozygous and not viable
68
How can genes within alternative orientations of inversion diverge?
Genes within alternate orientations of inversion can diverge dramatically even though there is no divergence anywhere else in the genome.
69
Where is there no recombination?
No recombination (between inversion orientations) within inversion region
70
What is the sequence divergence between independents and faeders?
Sequence divergence between Independents and Satellites (also Faeders):
* Inside inversions = ~1.4% (~= human- chimpanzee divergence!)
* Outside inversions = ~0% divergence.
71
What do cod have?
Cod have a large chromosomal inversion that is millions of years old.
72
Genes in the inversion influence what adaptation?
Genes inside the inversion influence whether cod are
adapted to ‘warmer’ or ‘colder’ water.
73
What happens to cod with both orientations?
Cod with both orientations of the inversion live off
Nova Scotia and interbreed.
74
What does not get scrambled by recombination?
Because recombination inside the inversion is suppressed, the ‘warm’ and ‘cold’ versions of the genes do not get scrambled by recombination.
75
Other major inversions cause what?
Several other major inversions in cod influence other traits, such as migration
76
What are 3 examples of polyploid species?
Wheat = hexaploid
Strawberry = octoploid
Fish = heptaploid
77
What is aneuploidity?
This is an increase or decrease in the number of individual chromosomes, e.g. trisomy, three copies of a chromosome.
78
What is polyploidity?
This is an increase in the number of sets of chromosomes, e.g. triploid, three copies of every chromosome in the genome
79
What is the difference in terms: trisomy vs. triploidy?
Trisomy = chromosome
Triploidy = genome
80
What does ploidy refer to?
‘ploidy’ refers to the total number of chromosomes
81
What does somy refer to?
‘somy’ refers to the number of particular chromosomes
82
What happened to a 47 chromosome individual?
47 (2n+1) - Gain of a single chromosome
83
What happened to a 48 chromosome individual?
48 (2n+2) - Gain of two homologous chromosomes
84
What happened to a 44 chromosome individual?
44 (2n-2) – Loss of both members of a pair of homologous chromosomes
85
What happened to a 45 chromosome individual?
45 (2n-1) - Loss of a single chromosome
86
What are the 4 types of aneuploidy?
The four most common types of aneuploidy in diploid (2n) individuals...
1. Trisomy
2. Monosomy
3. Nullisomy
4. Tetrasomy
87
What is trisomy?
Trisomy - Gain of a single chromosome: 2n+1 = 47
88
What is monosomy?
Monosomy - Loss of a single chromosome: 2n-1 = 45
89
What is nullisomy?
Nullisomy - Loss of both members of a pair of
homologous chromosomes: 2n-2 = 44.
- not tolerable in humans
90
What is tetrasomy?
Tetrasomy - Gain of two homologous chromosomes: 2n+2 = 48.
91
What happens if non-homologous chromosomes are altered (44 chromosomes)
We get a double monosomic individual
- this is less common
92
What happens if a non-homologous chromosome is altered (48)?
We get a double trisomic individual
- this is less common
93
What happens if the altered chromosome is homologous (44)?
This is when we get nullisomy
94
What happens if the altered chromosome is homologous (48)?
We get tetrasomy
95
What are the 2 main causes of aneuploidy?
1. nondisjunction in meiosis or mitosis
2. deletion of a centromere leading to chromosome loss
96
What is nondisjunction?
Nondisjunction – failure of homologous
chromosomes or sister chromatids to separate
97
Why does deletion of a centromere cause chromsome loss?
if the centromere is gone, then it cannot participate in cell division and gets lost
98
What happens when nondisjunction occurs in meiosis 1?
All gametes are altered, one half are missing and one half have extra chromosomes
99
What happens when nondisjunction occurs in meiosis 2?
We get 2 normal gametes, 1 with less material and one with more material
100
What is the result of fertilization of nondisjunction gametes?
We can get trisomy and monosomy
101
Is trisomy viable?
Trisomy: may be viable
102
Is monosomy viable?
Monosomy: usually not viable, except for sex chromosomes
103
What does trisomy 13 cause?
Patau syndrome; about 1 in 16000 newborns
104
What does trisomy 18 cause?
Edwards syndrome; about 1 in 5000 live-born infants
105
What does trisomy 21 cause?
Down syndrome; 1 in 800 newborns
106
What does monosomy X cause?
Monosomy X (XO) causes Turner syndrome; 1 in 2500 newborn girls
107
What does extra copies of the X chromosome cause (XXY or XXXY)?
Klinefelter syndrome; 1 in 500-1000 newborn males
108
What is the typical outcome of chromosomal abnormalities?
Chromosomal abnormalities, particularly autosomal trisomy, is thought to be the most common cause of spontaneous abortions or miscarriages
109
Where else do we observe XXY individuals?
Halifax researchers identified first known
cases of XXY individuals in 3 whale species
110
What is trisomy 21?
Trisomy 21: 3 copies of chromosome 21 (2n+1 = 47 chromosomes)
111
What accounts for Down syndrome cases?
Accounts for most cases of Down syndrome.
112
Where do most cases arise from?
Most cases arise from random nondisjunction during meiotic division.
113
What does the mother contribute in Down syndrome?
Mother contributes the extra chromosome in ~75% of cases.
- most trisomies are maternal in origin
114
When does incidence of trisomy 21 rise?
The incidence of trisomy 21 rises sharply with increasing
maternal age
Why?
- Possibly due to the fact that oocytes (eggs) are formed by birth, in arrested stage of meiosis
115
What happens in familial down syndrome?
An extra copy of chromosome 21 is attached to another chromosome (e.g. 14 or 15).
* Account for 3-4% of cases.
116
When does familial down syndrome occur?
Arise in offspring of parent who carry a chromosome that underwent Robertsonian translocation
(= exchange of long arms of non-homologous acrocentric chromosomes)
117
What is a translocation carrier of familial Down syndrome look like?
Translocation carrier
* 45 chromosomes, one of which is a translocation chromosome.
* Normal phenotype, does not have Down syndrome
118
How does aneuploidity incidence vary with chromosome number?
It becomes less common with the lower # of the chromosome
- this is because these are the longer/larger chromosomes and shifts in them are less tolerable
- this is why we see higher frequencies in smaller chromosomes
119
What do live births usually have?
Live birth usually have trisomy of smaller chromosomes (e.g. 21) or sex chromosomes.
120
What did Sabrina have and why did she survive until 21?
Sabrina had trusty of chromosome 9, and likely survived for many years because the trisomy was present as a mosaic (not all cells had it)
121
What do plants do better?
Aneuploidy: plants tolerate it better than animals
- usually viable, phenotype may be altered and fertility might be reduced
122
What is polyploidity?
For diploid (2n) individuals, polyploidy is the presence of more than two sets of chromosomes.
Triploids - 3n
Tetraploids - 4n
Pentaploids - 5n
ETC.
123
Where is polyploidy common?
Common in plants, less common in animals (some fishes, reptiles, amphibians and invertebrates). Not known in mammals and birds; presumably lethal.
124
What percentsjgew of evolution is attributed to polyploidy?
Polyploidy is very important in plants. 30-35% of Angiosperms evolved via some form of polyploidy.
125
What are the types of polyploids?
Autoplyploid and allopolyploid
126
What is an autopolyploid?
Multiples of the same genome.
e.g., autotetraploid - 4n
127
What is an allopolyploid?
Multiples of closely related genomes
e.g., allotetraploid - 4n; 2n from species i and 2n from species ii
128
When does autopolyploidy originate?
It can occur during mitosis or meiosis
- Nondisjunction of ALL chromosomes during mitosis in early embryo can produce autotetraploid
129
How are autotriploids made?
Diploid gamete + normal gamete = autotriploid (3n).
130
How are autotetraploids made?
Diploid gamete + Diploid gamete = autotetraploid (4n)
131
Autopolyploids are normally....?
Usually sterile or have reduced fertility (odd-numbered ploidy)
132
What gametes are produced by autopolyploids?
Most gametes produced are genetically unbalanced
133
How are sterile hybrids covered into fertile species?
To convert sterile hybrid into fertile ‘new’ species, need chromosome doubling.
134
The hybrid is ______ while unbalanced gametes are ______?
Hybrid is sterile.
o Unbalanced gametes are
nonviable.
135
What solves the fertility problem?
But if entire genome is
doubled by mitotic non-
disjunction, the fertility
problem is solved.
136
What is cell volume correlated with?
Cell volume correlated with nucleus volume, correlated with genome size.
137
Polyploids tend to have what?
Polyploids often have bigger leaves, fruits, seeds.
138
What is bread wheat derived from?
Bread wheat is a polyploid derived from 3 species.
139
What can we produce with polyploids in agriculture?
1. Production of larger fruits, e.g. strawberries and grapes.
2. Production of seedless fruit (sterile), e.g. bananas, grapes and watermelon.
140
Difference between wild and commercial strawberries?
- Wild strawberries (2n=14)
- Commercial strawberries (8n=56; allopolyploid), larger fruit.
141
Difference between wild bananas and commercial bananas?
- Wild diploid bananas (2n=22), lots of large seeds
- Commercial triploid bananas (3n=33, autopolyploid) are sterile.
Cannot produce viable gametes - undeveloped seeds.
142
When is polyploidy a problem?
Domestic bananas (mostly 3n = 33) are derived from 2 wild species: Musa acuminata (‘A’) and Musa balbisiana (‘B’).
* ‘Gros Michel’, Cavendish are AAA
* Most plantains are ABB or AAB
* World production = 100 Mt
* Most varieties derived from spontaneous hybrid polyploids found in the wild
* 2n gametes from one species, 1n gamete from another
143
What happened to Gros Michel?
In 1950s & 1960s, Gros Michel wiped out by ‘Panama disease’ (Fusarium).
144
What replaced gros Michel?
Replaced by resistant
Cavendish.
145
What happened in the 1980s?
In 1980s, a new strain of
Fusarium, ‘Tropical Race 4’
appeared in Malaysia, now
spreading around world.
Cavendish has no resistance
146
Have we detected any aneuploidies in human remains?
Several aneuploidies (trisomy 18, trisomy 21, X0, XXY) have been
detected in ancient humans.
147
How did we detect aneuploidy in ancient humans?
These detections were obtained by comparing ‘dosage’ of DNA sequences from different
chromosomes.
148
How are mutations rare?
Rare because DNA replication
occurs with high fidelity.
149
How are mutations common?
Common because there is a lot
of DNA being replicated! (e.g.,
~64 new mutations/human
generation
150
What are mutations the source of?
Ultimate source of all genetic
variation.
151
How many mutations per generation are there?
~64 mutations/generation is just an
estimate. The actual number varies a lot.
152
What do most new mutations come from?
Most new mutations in human offspring come from the father
153
What strongly influences the number of mutations?
~~4x more from father than from mother, but the number is strongly influenced by age of the father
154
What do offspring of older fathers have and why?
Offspring of older fathers have more
mutations.
* Reason is that spermatogonial stem cells keep dividing through entire adult life (opposite of situation in mothers). As father gets older, mutations in stem cells accumulate.
155
What are somatic mutations?
Somatic mutations are not transmitted from one generation to another.
156
What are germ-line mutations?
Germ-line mutations may be transmitted to ~50% of offspring
157
What are point mutations?
Point mutations (base substitutions)
can be classified into 3 categories,
based on effect
158
What are silent point mutations?
Silent (aka synonymous): no change
in amino acid (aa) sequence. Happens
in reading frames because of
redundancy in genetic code.
159
What are missense point mutations?
Missense (aka nonsynonymous):
mutation causes 1 aa to be
substituted for another, changing the
aa sequence.
160
What are nonsense mutations?
Nonsense: An amino acid codon is
converted to a stop codon.
161
What do indels do?
Indels cause frameshifts that alter
reading frames, creating either
nonsense or missense effects on
protein
162
What happens when indels occur in multiples of 3?
when indels occur as
multiples of 3 nucleotides. In such
cases the amino acid sequence will
change (either become shorter or
longer), but the reading frame is
preserved.
163
What is the effect of indels outside the reading frame?
Indels outside of reading frames
usually have no effect on
phenotype
164
What happens if a mutation causes loss-of-function?
Loss-of-function: protein function
completely or partly lost. Recessive
inheritance.
165
What happens if a mutation causes gain-of-function?
Gain-of-function (aka radical): new
gene product, or gene product in
‘wrong’ tissue. Dominant
inheritance
166
What happens if a mutation causes a neutral change?
Neutral: Missense mutation that
results in non-significant change in
protein function, because one
chemically similar amino acid
substituted for another, or occurs in
a part of the protein that is not
important for function.
167
What is the difference between transitions and transversions?
Because of the nature of the chemical changes leading to mutations,
transitions are more common than transversions, even though there are twice as many possible transversions.
168
What are transitions?
Transitions are when one purine becomes the other or one pyrimidine becomes the other.
- G becomes A
- C becomes T
- and vice versa
169
What are transversions?
This is when a purine becomes a pyrminidine or vice versa
170
Instances of purine becoming pyrimidine?
A becomes C
A becomes T
G becomes C
G becomes T
171
Instances of pyrimidine becoming purine?
T becomes A
T becomes G
C becomes A
C becomes G
172
What does a forward mutation do? What is the role of a reverse mutation?
Forward mutation: alters wild phenotype
Reverse mutation changes mutant phenotype back to wild phenotype
173
What are true reversions?
Two mutations - get forward then goes back to normal.
174
What is a suppressor mutation?
Suppressor mutations, where the first mutation is suppressed by a
second mutation
- first is forward
- second is reverse (not same as forward)
- second mutation suppresses expression of the first
175
What are the two types of suppressor mutations?
1. Intragenic suppressor mutation (in the same gene).
2. Intergenic suppressor mutation (in a different gene)
176
Intragenic suppressor mutation works how?
1. A missense mutation alters a single codon
2. A second mutation at a different site in the same gene
3. this may... restore the original amino acid
- INTRA = WITHIN
177
Intergenic suppressor mutation?
1. wild type
2. first mutation, cannot bind the inactive protein complex
3. second mutation acting as suppressor, allows the protein complex to be activated and bind
178
How do mutations happen?
Spontaneously or induced by physical and chemical agents.
179
What are the three types of spontaneous mutations?
1. Tautomeric shifts (base tautomers) during DNA replication.
2. DNA strand-slippage during DNA replication.
3. Misalignment of homologous chromosomes during crossing-
over (recombination) at meiosis I.
180
What are tautomeric shifts?
This can happen due to a proton shift, where they jump in the secondary position.
181
What is a rare form of tautomers?
H+ shift to the oxygen, which is rare because it is more unstable than the "normal" state
182
What do tautomers affect?
They affect base pairing
- C will bind A, not normal in complementary base pairs
- T will bind G, not normal
183
What do base tautomers cause?
Base tautomers cause incorrect base-pairing during DNA replication
184
What does an insertion or deletion cause?
An insertion or deletion owing to slipped-strand mispairing
during DNA replication
185
How does strand-slippage work?
1. newly synthesized strand loops out
2. this results in the addition of one nucleotide on the new strand
3. template stand loops out
4. results in the omission of one nucleotide on the new strand
186
What is the nature of misalignment spontaneous mutation?
Repetitive nature, nor hard for chromosomes to costumes not get aligned properly to cause these 3 part mutations
187
How does misalignment work?
1. if homologous chromosomes misalign during crossing over
2. one crossover product contains an insertion
3. the other has a deletion
188
How does radiation cause mutation?
* Ionizing radiation: cosmic rays (high energy particles), X-rays and gamma rays (electromagnetic waves with very short wavelength).
* Ultraviolet radiation from sunlight.
189
What does ionizing radiation create?
Ionizing radiation creates free radicals, dislodging electrons that causes molecules to be very reactive, making the DNAb structure damaged
190
What is the result of ionizing radiation?
Result: change stable molecule into a free radical or an ion , which can
alter the structure of bases and break phosphodiester bonds in DNA.
191
What causes ionizing radiation?
Cosmic, gamma or X-rays
- causes electron to be dislodged
192
What foes UV radiation damage?
It does not make it past the skin, but does do great damage to the skin
193
What is UV radiation?
Ultraviolet (UV) radiation is electromagnetic radiation of lower
energy than ionizing radiation. Can still generate free radicals under
some circumstances, but less likely to do so than higher energy
radiation.
194
What are the common sources of UV radiation?
Most common source: the sun.
* Can be generated by various types of lamps, e.g., mercury vapour
lamps.
195
What is formed by UV radiation?
Pyrimidine dimers. (TT or CC) can be induced by exposure to UV radiation.
- cross linkage of adjacent pyrimindines causes a kink in structures
196
What do pyrimidine dimers block ?
They can block DNA replication
197
What corrects damaged DNA?
DNA repair enzymes correct the damaged DNA.
198
How does nucleotide excision repair occur?
* Protein recognizes mismatches
* Unwinds DNA in area of
mismatch
* Excises out nucleotides
* Fills in correct nucleotides
199
What is xeroderma pigmentosum?
An autosomal recessive genetic disorder of DNA repair
* The ability to repair mutations caused by ultraviolet (UV) light is
deficient.
* deficient in repair mechanisms
200
What is the role of laminar flow hood sterilization?
This is a UV light mechanisms that sterilizes things or can have other applications
- Other applications include water purification for drinking, or to
disinfect sewage
201
What are the three categories of chemical mutagens?
* Base analogs.
* Base modifying agents.
* Intercalating agents.
202
What are base analogs?
Chemicals that appear similar to the normal bases in DNA, but causes incorrect base-pairing and introduce point mutations during DNA replication
- chemicals that aren't normal DNA bases, but similar enough too be added into the growing DNA strand.
203
What is 5-bromouracil?
This is a nucleotide analog that resembles both thymine and cytosine, therefore can bind adenine and guanine in certain situations.
204
What does 5-bromouracil normally base-pair with? When does this change?
Like thymine, 5-bromuracil normally base pairs with adenine, but when ionized it will base pair with guanine
- flicker between 2 diff BP states
205
What are base modifying agents?
Chemicals that modify groups on the normal bases in DNA that result in incorrect base-pairing and introduce point mutations during DNA replication
206
What is the role of base modifying mutagens?
Point is that these chemicals can alter to unused base in every case leading to a transition
207
What are intercalating agents?
Chemicals that distort the normal stacking of bases in DNA resulting in insertion or deletion of a single base-pair during DNA replication
- flat chemicals that slide in between bases to cause trouble
208
How do intercalating agents appear?
They are flat molecules that insert between adjacent bases in DNA, look similar to one another with 3 rings and many methyl and amine groups
209
Where do intercalating agents insert?
Intercalating agents insert
between adjacent bases
distorting them by 0.68 nm, the
size of a base.
210
What does DNA polymerase do to intercalated DNA?
First round of DNA replication,
the DNA polymerase randomly
selects any nucleoside triphosphate opposite the intercalating agent.
* Result: frame-shift due to
insertion of a base.
211
What is the problem regarding chemicals and how mutagenic they are?
There is uncertainty and
disagreement about how many
man-made chemicals are in use,
but there are lots of them.
* Need to know which ones pose
mutagen/carcinogen risks.
212
What is the Ames test?
A simple method to measure the reversion of a mutant His- Salmonella
bacterial strain to His+ Salmonella wild-type strain by potential
mutagen
- an assay for chemical mutagenicity
213
Were can His- salmonella not grow?
His- Salmonella cannot grow on minimal medium lacking the essential
amino acid, histidine.
214
Where does His+ grow?
His+ Salmonella will grow on minimal medium.
215
What does increased reversions indicate?
Increased reversions of His- to His+ Salmonella indicate the chemical is
a mutagen, and thus, a potential carcinogen.
216
What does the inclusion of rat liver enzymes cause?
Inclusion of rat liver enzymes
to mimic the chemical modification of potential mutagens in the human body.
- Liver enzymes could make the chemical more or less mutagenic.
217
What do we need to analyze when looking at the Ames test?
The number of revertant colonies
218
What has the Ames test been able to identify?
Ames test has identified numerous human-
made chemicals as mutagens (and therefore,
potential carcinogens)
219
What has the Ames test led to?
Has led to many of these chemicals being withdrawn from or restricted in commercial use.
BIOL2030
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