Download Chapter 11 - Chromosome Mutations

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Chapter 11 - Chromosome Mutations
Questions to be considered:
1) how are changes in chromosome number (different from
haploid or diploid) defined?
2) how do changes in chromosome number occur?
3) what are the meiotic consequences of changes in chromosome
number?
4) what are the phenotypic consequences of changes in
chromosome number?
5) How do changes in chromosomes structure affect meiotic
pairing?
6) How do changes in chromosome structure affect
recombination frequency?
Terminology:
ploidy: number of chromosomes in an organism relative to a set of
homologues
euploidy: having a multiple of a complete set of homologues
aneuploidy: having an incomplete set of homologues
monoploid: a cell having only one chromosome set (usually an
aberration), or an organism composed of such cells (a set of
homologues = x)
diploid: a cell having two chromosome sets, or an individual having
two sets of chromosomes sets in each of its cells (two monoploid sets
= 2x)
triploid: a cell having three chromosome sets, or an organism
composed of such cells (three monoploid sets = 3x)
polyploid: a cell having three or more chromosome sets, or an
organism composed of such cell (greater than 2x)
autopolyploidy: all sets of chromosomes originate from the same
species
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allopolyploidy: some sets of chromosomes originate from different
species
nondisjunction: the failure of homologues (at meiosis) or sister
chromatids (at mitosis) to separate properly to opposite poles
monosomic: a cell or individual that is basically diploid but that has
only one copy of one particular chromosome type and thus has
chromosome number 2n-1
nullisomic: a cell or individual with one chromosomal type missing,
with a chromosome number such as n - 1 or 2n - 2
trisomic: basically a diploid with an extra chromosome of one type,
producing a chromosome number of the form 2n + 1
In polyploids x is not equivalent to n (see table 8-1)
x= a set of chromsomes with one member of all homologous pairs
example - wheat is a hexaploid (6x) = 42 chromosomes (x = 7)
- haploid number (chromosomes in gamete) = 21
Examples of Changes in Ploidy
MONOPLOID
- males of bees and wasps
- gametes produced by mitosis
- generation of plants from pollen
- select for mutations in a monoploid (which is sterile)
- double the chromosome number using colchicine
POLYPLOIDS
1) autopolyploids – all sets of chromsomes are from the same species
2) allopolyploids – sets of chromosomes are from different species
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Triploids
- usually sterile (commercially developed bananas, oysters)
- meiotic pairing possibilities:
1) all three chromosomes form a group = TRIVALENT
2) two chromosomes pair (BIVALENT) and one chromosome
is unpaired (UNIVALENT)
TRIVALENT
Pairing
Possibilities
BIVALENT
UNIVALENT
(refer to Figure 11-5)
- two chromosomes move to one pole, one chromosome moves to the
other pole
- for each chromosome trio, there what chance of one chromosome
moving to a given pole?
results: if there are x chromosomes, the chance of one chromosome
from each trio going to the same pole is 1/2x-1
- if x = 8, p(normal gamete) = 1/128
conclusions: most gametes are aneuploid
AUTOTETRAPLOID (two sets of identical chromosomes)
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(refer to Figure 11-7)
segregation
- prediction requires a stable pairing pattern
e.g. assume bivalent pairing in an individual of genotype aaAA (a is
closely linked to the centromere)
question: what is the probability of progeny of genotype aaaa (the
recessive phenotype)?
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Pairing
1
2
3
1
2
3
4
A
4
A
a
a
1
3
2
4
1
4
2
3
A
Gametes Produced by
Random Spindle Attachment
1 +3
2 +4
Aa
Aa
1 +4
2 +3
Aa
Aa
1 +2
3 +4
AA
aa
1 +4
2 +3
Aa
Aa
a
1 +2
3 +4
AA
aa
A
a
1 +3
2 +4
Aa
Aa
A
a
a
A
a
A
a
A
conclusion: p(aaaa) =
=
ALLOPOLYPLOIDS (multiple chromosome sets from different species)
e.g. radish (n1 = 9)
x cabbage (n2 = 9) (Figure 11-8)
The Evolution of Wheat (an allopolyploid) (Figure 11-10)
ANEUPLOIDS (missing part of a chromosome set)
- generated through nondisjunction (chromosomes do not segregate at
Meiosis I or chromatids do not separate at Meiosis II) (Figure 11-13)
--------> n + 1 and n - 1 gametes
Monosomic: only one copy of a chromosome is present
- 2n - 1 (n - 1 gamete + n gamete)
Nullisomic: has no copy of a chromosome
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- 2n - 2 = (n -1 + n-1 gametes)
Trisomic: has an extra copy of a chromosome
- 2n + 1 = (n + 1 + n)
Human Aneuploids
- autosomal aneuploids are mostly lethal
- sex chromosome aneuploids are tolerated
examples:
1) Turner Syndrome (XO) - monosomic for sex chromosome
- occurrence = 1/2000 live births
- PHENOTYPE: sterile females that are short in stature
- X chromosome may come from the father or mother
(Figure 11-14)
2) Klinefelter Syndrome (XXY) - trisomic for sex chromosomes
- occurrence = 1/1000 live births
- PHENOTYPE: sterile males
(FIGURE 11-16)
3) Down Syndrome - trisomy 21 (autosomal)
- occurrence = 15/10 000 live births (related to age of mother)
(FIGRUE 11-17)
- other chromosomal abnormalities are produced
- 7.5% of conceptions are spontaneously aborted due to chromosomal
abnormalities
CHROMOSOMAL REARRANGEMENTS
Types of rearrangements:
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Balanced: no DNA is lost or gained, only gene arrangement is altered
e.g. inversions and translocations
Imbalanced – DNA is lost or gained, e.g. deletions and duplications
-
caused by chromosome breakage (e.g. induced by ionizing radiation)
and rejoining of fragments in an altered configuration (Figure 1119A)
-
caused by crossing-over between repetitive DNA (Figure 11-19B)
1. Deletion: removal of a chromosomal segment from a chromosome set
• characteristics:
1) following a deletion, chromosome is shortened
2) often lethal when homozygous (maintained as heterozygote)
3) during prophase I, heterozygous individuals form a deletion loop
(Figure 11-21, 11-28)
b
a
c
d
e
A
C
D
E
4) heterozygotes show reduced recombination
A
a
b
C
D
E
c
d
e
- there is NO recombination within a deleted region
•
if a-c distance is normally 10 map units (i.e. the frequency of
recombination = 10%) and a deletion heterozygote has an a-c
recombination frequency of 3%, then a deletion of 7 map units
(including b) has occurred
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5) pseudodominance of recessive alleles in heterozygotes
Example:
An individual is heterozygous for a deletion involving Bar-eyed gene in
Drosophila (i.e. it has reduced eyes). The homozygous condition is
lethal.
How much of the chromosome is missing?
Approach: Cross individual heterozygous for the deletion to an
individual homozygous for recessive mutations near Bar gene (an
example is forked)
Bar eye
B
Phenotype
F? del
F
bar-eyed, wild type
X
B
B
f
f
wild type, forked
Conclusion: if a recessive mutation appears dominant
(pseudodominance) when heterozygous with a deletion, the gene must
be included within the deletion
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If a series of deletions spanning known regions is available, a
recessive mutation can be mapped by combining it with each deletion
and determining with which it appears pseudodominant (Figure 11-29)
Example: A recessive mutation (c) causes curled wings in Drosophila.
The C gene is found on chromosome 1
cc = curled wings
C_ = wild type wings
Approach: cross to a series of lines heterozygous for deletions in
different regions of chromosome 1
Result: F1 is heterozygous for deletion and c
- if F1 shows curled phenotype, pseudodominance is displayed and the
deletion therefore includes C
-therefore, C is in the region
Duplications
-a region of a chromosome is copied elsewhere
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- duplicate copies, allow divergence of one copy from its original
function ---> gene family
adjacent duplications
pairing in duplication heterozyg
-3 copies (2 in one chromosome, one in homologue)
1) between adjacent regions
2) between different chromosomes
Inversions
-chromosome broken (= breakpoint) and rejoined in opposite
orientation
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- information isn’t lost, therefore no consequences to homozygous
individual unless the breakpoint interrupts a gene (Figure 11-20)
paracentric - inversion excludes centromere
A
original
A
paracentric inversion
B
C
D
C
D
B
E
E
pericentric - inversion includes centromere
original
A
B
A
C
C
B
D
D
pericentric inversion
Meiosis in inversion heterozygotes (Figure 11-21
Case 1 - heterozygous for a paracentric inversion
A
B
C
A
D
C
D
B
E
E
Consequences:
1) meiosis in an individual heterozygous for a paracentric inversions
(see figure 8-22)
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Consequences
-recombination within the inversion loop produces acentric and
dicentric recombinant chromosomes
-acentric chromosome is lost
-dicentric chromosome is broken causing deletions - inviable
-no recombinant products are viable
therefore, recombinants produced within the inversion =
therefore, apparent distance between inversion breakpoints =
experiment:
•
cross a plant with dominant alleles at 5 genes to a plant with
recessive alleles at 5 genes, which also carries a paracentric
inversion
•
cross the F1 heterozygote to a recessive homozygote (test cross)
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A
B
C
D
E
A
B
C
D
E
5 5 5 5
x
d
c
b
e
a
d
c
b
e
5 5 5
5
F1 heterozygote
a
A
B
C
D
a
d
c
b
5
5
E
e
Results: percentage of recombinants between pairs of genes seen in
the test cross progeny
A
B
C
D
E
A
0
B
8
0
Conclusions:
C
8
0
0
D
8
0
0
0
E
12
4
4
4
0
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Case 2 -Meiosis in an individual heterozygous for a pericentric
inversion (Figure 11-23)
2) pericentric inversions
-recombination within the inversion loop generates duplications and
deletions
-gametes carrying these recombinants are inviable, or produce inviable
zygotes (reduced fertility)
-recombinants produced within the inversion = 0, distance between
breakpoints = 0
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Translocations
-reciprocal translocation: a segment of one chromosome is exchanged
with a segment from a nonhomologous chromosome
-as with inversions, may be no phenotypic consequences to the
homozygous individual
-heterozygotes will have reduced fertility due to abnormal chromosome
pairing and segregation
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Figure 1124
segregation at meiosis produces:
1) two normal chromosomes (N1 + N2) - viable
2) two translocated chromosomes (T1 + T2) - viable
3) T1 + N1 - inviable
4) T2 + N2 - inviable
-events are equally likely, therefore 50% of gametes are inviable =
semisterile