1
Q
What are chromosome variations and what are the two general types?
A
- permanent chromosomal changes
- can be passed on to offspring if they occur in cells that will become gametes (‘germ-line’)
two types
1. chromosome rearrangement: changes in structure of individual chromosomes
2. variation in chromosome numbers: changes in number of chromosomes, one or more individual chromosomes are added or deleted
2
Q
What are the 4 types of chromosomal rearrangements?
A
- deletions
- duplications
- inversions
- translocation
3
Q
Chromosomal rearrangements: deletions, what are they?
A
- loss of a segment, either internal or terminal, from a chromosome
- arise by terminal-ends breaking off (one break) or internal breaking and rejoining of incorrect ends (two breaks)
- OR arise by unequal crossing over
- major effect: loss of genetic information (importance depends on what, and how much is lost)
4
Q
How are deletions detected?
A
deletion loops can be detected during meiosis, and deletions can also be detected by a variety of molecular methods that detect lower heterozygosity or gene dosage
*looping out must occur for homologous pairing during meiosis
5
Q
Consequences of deletions
A
- loss of DNA sequences
- phenotypic effects depend on the size and location of deleted sequences
- deletions that span a centromere result in an acentric chromosome that will most likely be lost during cell division, may be lethal
- may allow expression of alleles that are normally recessive = pseudodominance
- may affect gene dosage
- when a gene is expressed, functional protein is normally produced at the correct level or dosage
- some genes require two copies for normal protein production; if one copy is deleted mutant phenotype can result = haploinsufficiency
6
Q
What are duplications?
A
- repetition of a chromosome segment
- tandem duplication is simplest form
- single gene or cluster of genes can be duplicated
- nothing is lost, duplication often have little/ no effect on phenotype/viability
- offspring usually viable
- sometimes excess/unbalanced dosage of gene products can cause problems
- important in evolution => extra copies of genes provide raw material for new genes and adaptations
- about 5% of human genome = duplications
7
Q
Origins of duplications
A
- unequal crossing over of misaligned chromosomes during meiosis generates duplications (and deletions, in other chromosomes)
8
Q
Detection of duplications
A
- can be visualized with staining
- by other various molecular methods that detect higher gene dosage
9
Q
Evolutionary consequences of duplications
A
1) both copies of the duplicated gene remain the same => redundancy; alter gene dosage, could have an effect
2) one copy becomes inactive => pseudogene (not functioning anymore)
3) one copy acquires a new function => neofunctionalization (new function), gene families
10
Q
Consequences of duplication: neofunctionalization
A
- source of new genes
- creates multigene families
- ex: globulin gene family
11
Q
Consequences of duplication: gene dosage
A
- can affect phenotype
- amount of protein synthesized is often proportional to number of gene copies present (extra genes lead to extra proteins)
12
Q
What are inversions?
A
result of two breaks on a chromosome followed by reinsertion in the opposite orientation can produce an inversion
- pericentric (around)
- paracentric (beside)
13
Q
What is the effect of inversions on phenotype?
A
- often none
- sometimes can affect phenotype due to change in position of gene(s)
14
Q
Inversion consequences: position effects
A
- change in position can alter expression
- genes in/near chromatin may not be expressed
15
Q
Suppression of recombination
A
- a consequence of inversion
- no crossing over: gametes produced usually viable because genetic info not lost or gained
- crossing over: outside of inverted region, viable gametes; within inverted region, some nonviable gametes and reduced recomb frequency
crossing over with paracentric inversion: dicentric chromatid, dicentric bridge breaks as centromeres are pulled apart, resulting recombinant gametes are nonviable because they are missing genes (therefore will never see these progeny)
crossing over with pericentric: resulting recombinant gametes are nonviable because genes are missing or are present in too many copies
16
Q
Translocation
A
- exchange of segments between non-homologous chromosomes, or to a different region on same chromosome
- translocations between chromosomes can be reciprocal (two-way) or non-reciprocal (one-way)
- if no genetic material lost, considered balanced translocation
17
Q
Consequences of reciprocal translocation
A
- translocations also change position of genes (like inversions)
- can alter expression of gene(s) because of association with different proteins, or formation of new gene products (fusion proteins)
18
Q
What does a lack of recombination within inversions mean?
A
genes within the inversions are free to diverge to produce different adaptations
19
Q
Aneuploidy
A
increase or decrease in number of individual chromosomes (e.g., trisomy)
20
Q
Polyploidy
A
increase in number of sets of chromosomes (e.g., triploid, three copies of every chromosome)
21
Q
What are the four most common types of aneuploidy?
A
trisomy: gain of a single chromosome (2n+1 = 47)
monosomy: loss of a single chromosome (2n-1 = 45)
nullisomy: loss of both members of a pair of homologous chromosomes (2n-2 = 44)
tetrasomy: gain of two homologous chromosomes (2n+2 = 48)
22
Q
Can aneuploidy be homologous and non-homologous?
A
yes, the non-homologous variations are less rare though
23
Q
Origins of aneuploidy
A
- nondisjunction in meiosis or mitosis (failure of homologous chromosomes or sister chromatids to separate
- deletion of a centromere leads to chromosome loss
24
Q
Primary Down Syndrome
A
- 3 copies of chromosome 21
- accounts for most cases of down syndrome
- most cases arise from random nondisjunction during meiotic division
- most trisomies are maternal in origin
- incidence of trisomy 21 increases sharply with increasing maternal age
25
Familial down syndrome
- extra copy of chromosome 21 is attached to another chromosome
- arise in offspring of parent who carry a chromosome that underwent Robertsonian translocation (exchange of long arms of non-homologous arocentric chromosomes)
Translocation Carrier:
- 45 chromosomes, one of which is a translocation chromosome
- normal phenotype, does not have down syndrome
- in terms of dosage, has right amount of chromosome 21
26
Why are certain aneuploidies more survivable than others?
it depends on chromosome length; longer chromosomes contain more genes, thus removing/adding a chromosome has a big impact
27
Do plants tolerate aneuploidy better than animals?
yes; they are usually viable but may have an altered phenotype and fertility is reduced
28
Why is polyploidy important in plants?
30-35% of angiosperms evolved via some form of polyploidy
29
What are the 2 types of polyploidy?
autopolyploid: multiples of the same genome
allopolyploid: multiples of closely related genomes (e.g., 4n; 2n from species 1, 2n from species 2)
30
Origins of autopolyploidy
nondisjunction of ALL chromosomes during mitosis in early embryo can produce an autotetraploid
nondisjunction of ALL chromosomes during meiosis produces diploid gametes (unreduced gametes)
diploid + normal gamete = 3n
diploid + diploid = 4n
31
Effects of autoploidy
- usually sterile
- most gametes produced are unbalanced
32
How are allopolyploid species generated?
- gametes (n) from 2 species fuse to create a hybrid (2n)
- if all gametes of F1 generation undergo mitotic nondisjunction to double each chromosome, hybrid plant is sterile (4n)
33
What is the significance of polyploids in agriculture?
having a larger genome leads to larger cell size => larger plant size
34
Why are mutations considered rare and common?
rare: DNA replication occurs with high accuracy
common: a LOT of DNA is being replicated
*ultimate source of all genetic variation
35
Somatic vs germ-line mutation
somatic: non transmitted from one generation to another
germ-line: may be transmitted to 50% of progeny
36
How are mutations classified based on their effect on amino acid sequence of protein?
Point mutations
- silent
- missense
- nonsense
Indels
- cause frameshifts that alter reading frames (unless indels occur in multiples of 3), creating either nonsense or missense effects on protein
- indels outside out reading frame often have no effect on phenotype
37
How do mutations effect functional phenotype?
- loss of function: protein function completely/partly lost (recessive inheritance)
- gain of function (aka radical): new gene product, or gene product in 'wrong' tissue (dominant inheritance)
- neutral: missense mutation resulting in non-sign. change in protein function (due to similar amino acid, or mutation is in part of protein not super needed for function)
38
Mutations: transitions vs transversions
Transitions: from purine to purine, or pyrimidine to pyrimidine
Transversions: purine to pyrimidine, pyrimidine to purine
* transitions are much more common despite having less options because of the nature of chemical changes leading to mutations
39
Forward and reverse mutations
Forward
- alters wild phenotype
Reverse
- changes mutant phenotype back to wild phenotype
- true reversions
- suppressor mutations, where second mutation suppresses first mutation
- intragenic suppressor (in same gene)
- intergenic suppressor (in different gene)
40
What are the two ways in which mutations can happen?
1. spontaneously
2. induced by physical and chemical agents
41
What are the 3 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
42
Tautomeric shifts during DNA rep
- each base has a tautomer (common and rare forms)
- the rare forms can cause the base to base pair with a different base than usual (e.g., C with A, G with T)
- in second round of DNA rep, a mutation will arise (slide 17 10.3)
43
DNA strand-slipping
- a newly synthesized strand slips out (in a repetitive sequence)
- result is the addition of one nucleotide on the new strand
- OR template strand loops out
- result is the omission of one nucleotide on the new strand
44
Misalignment of homologous chromosomes during crossing-over at meiosis I
- misalignment during crossing over leads to one crossover product containing an insertion, and the other has a deletion
45
What are mutagens? Give examples
- agents that cause mutation
- radiation: ionizing radiation (cosmic rays, X-rays, gamma rays)
- chemical mutagens: base analogs, base modifying agents, intercalating agents
46
How does ionizing radiation lead to mutation?
- ionizing radiation creates free radicals, which can alter the structure of bases and break phosphodiester bonds in DNA
47
How does ultraviolet radiation cause mutations?
- induces thymine dimers in DNA, which can block replication
- DNA repair enzymes can correct this damaged DNA
- protein will recognize mismatches
- unwinds DNA in area of mismatch
- excises out nucleotides
- fills in correct nucleotides
48
How do base analogs cause mutation?
base analogs are chemicals that appear similar to normal bases in DNA, but cause incorrect base-pairing and introduce point mutations during replication
ex: 5-bromouracil (looks like T and C)
- normally pairs with A, but will pair with G when ionized
- can change base pairing in DNA rep
49
Base modifying agents as mutagens
chemicals that modify groups on the normal bases in DNA that result in incorrect base-pairing and introduce point mutations during DNA rep
50
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
- they are planar molecules that insert between adjacent bases in DNA => distorts them
- first round of DNA rep, the DNA polymerase randomly selects any nucleoside triphosphate opposite the intercalating agent
- result: frame-shift due to insertion of a base
51
How can we determine what chemicals are/ are not mutagens?
using the Ames test: an assay for chemical mutagenicity
52
What is the principle and objective of the Ames test?
objective: determine if a particular chemical causes mutations
principle: test if the chemical causes reversion mutations in bacteria
- if his- salmonella grows on medium deficient in histidine in presence of chemical, then the chemical is a mutagen
53
Why were rat enzymes included in the Ames test?
to mimic the chemical modification of potential mutagens in the human body
- could make the chemical more or less mutagenic
BIOL 2030
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