1. Evolution of eukaryotic genomes
Lecture 5 – Chromosomal mutations II
Davita 2008

2. Chromosome mutations Important
Insight into gene function
Insight into meiosis and chromosome architecture
Useful tools for genetic manipulation
Insight into evolutionary processes
Cause abnormalities in cell and organisms function
Usually divided into to groups
Changes in structure
Rearrangements of existing DNA
Changes in number
Numbers of DNA molecules change

3. Changes in chromosome number
Aberrant euploidy
changes in whole chromosome sets
Aneuploidy
changes in parts of chromosome sets

4. Abberant euploidy

5. Aberrant euploidy Euploid -organisms with basic chromosome set
Normal euploid organisms have both diploid (somatic) haploid (gametes) cells
Monoploid – only one chromosome set in a usually diploid organism
Polyploids -more than two chromosome sets
Name
Designatioin
Constitution
No. of chromosomes
Monoploid n
ABC 3
Diploid 2n
AABBCC 6
Triploid 3n
AAABBBCCC 9
Tetraploid 4n
AAAABBBBCCCC 12
Monosomic
2n-1
ABBCC 5
AABCC
AABBC
Trisomic
2n+1
AAABBCC 7
AABBBCC
AABBCCC

6. Aberrant euploidy - Monoploids
Male bees, wasps and ants are monoploid
Males develop by parthenogenesis from unfertilized egg cells
Meiosis is abnormal – no pairing partners
Monoploids are usually sterile
Bees, wasps and ants produce gametes by mitosis
Davita 2008

7. Aberrant euploids - polyploids
Correlation between copies of chromosome set and organism size
Higher the ploidy level, larger the size
Autopolyploids
Multiple sets from within one species
Allopolyploids
Sets from two or more different (but closely related) species
Chromosomes are only partly homologous -homeologous

8. Aberrant euploids - autopolyploids
Triploids usually autopolyploids
Arise spontaneously
Can be constructed by crossing a tetraploid (4n) and a diploid (2n)
Usually sterile due to pairing problems at meiosis
Pairing only takes place between two of the 3 chromosomes of each type
Chromosome numbers between haploid and diploid number
Aneuploids
not usually fertile

9. Aberrant euploidy - autotetraploids
Doubling of 2n to 4n
Spontaneous or chemically induced –colchicine
S-phase occurs, but not segregation or division
A nuclear membrane forms around the double set of chromosomes
Treatment with colchicine for another cell cycle results in octaploids (8n)

10. Aberrant euploids – autotetraploids
Since 4 is even – meiosis can be normal
Depends on pairing
Viable gametes are diploid
Upon fusion, zygote will again be autotetraploid

11. Aberrant euploids - allopolyploids
Hybrid of two or more species with two or more copies of the input genomes
Karpechenko (1928) crossed cabbage (Brassica) with radish (Raphanus)
Both species had 18 chromosomes and are closely related
Hybrid was functionally sterile since 9 chromosomes did not synapse
Part of the hybrid produced seeds which developed into fertile plants with 36 chromosomes
Result of spontaneous chromosomal doubling to 2n1 + 2n2 in one region of the hybrid

12. Aberrant euploids - allopolyploids
Major force in speciation of plants
Brassica – 3 species naturally hybridized to form new amphidiploid species

13. Aberrant euploids - allopolyploids
Bread wheat (Triticum aestivum) 6n=42
Two sets of 3 ancestral genomes
Pairing is between homologues from within an ancestral genome
Always 21 bivalents

14. Aberrant euploidy – Polyploidy in animals
salamander
Reproduce by parthenogenesis
Multiple modes of reproduction including a sexual cycle
Triploid oysters (sterile) used since do not go through a spawning cycle which makes diploids inedible
flatworm
leech
brine shrimp
oyster

15. Aneuploidy

16. Aneuploidy Chromosome number is abnormal
Chromosome number differs from wild type by part of the chromosome set
Can have either more or less chromosomes than wild type
Monosomic
2n-1
one copy of one chromosome, rather than normal diploid
Trisomic 2n+1
Nullisomic 2n-2
Disomic n+1
Refers to autosomes
Sex chromosomes – listed as multiple letters
XXY
XYY
XXX XO

17. Nondisjunction During meiosis is the usual cause of aneuploidy
Failure of chromosomes or chromatids to segregate properly
Produces gametes with abnormal cell numbers
Occurs spontaneously due to a failure of cellular processes
Usually occurs during meiosis I
Bivalents joined by CO
Mutagens which dec. CO also inc. nondisjunction

18. Monosomics (2n-1) Monosomics for all human autosomes die in utero
Sex chromosome monosomy (44 +1X) gives Turner syndrome
Sterile females, short, web of skin between neck and shoulders
1 in 5000 female births

19. Trisomics (2n+1) May be viable and fertile
Trisomic chromosomes form a group of three during meiosis
Klinefelter syndrome
XXY – sterile
Down syndrome
Trisomy 21
Life expectancy 17 yrs
Patau syndrome
Trisome 13
Life expectancy 130 days
Edwards syndrome
Trisomy 18
Life expectancy few weeks

20. Gene Balance Plants more tolerant of aneuploidy than animals
Datura stramonium (jimsonweed)
n = 12
polyploid (n=24) is larger
aneuploidy of each of the 12 different chromosomes results in a unique change

21. Gene Balance Why??? Aneuploids much more abnomal than polyploids
Aneuploidy for different chromosomes has different effects
Monosomics usually more affected than trisomics
Why???
Davita 2008

22. Gene balance
Euploid ratio of genes on any one chromosome to another chromosome is 1:1 (100%)
Holds true for monoploids, diploids tetraploids etc.
But not aneuploids
50% difference from WT for monosomics
150% difference from WT for trisomics
Aneuploid genes are out of balance

23. Gene balance
Rate of transcription directly proportional to number of DNA molecules
More copies = more transcripts = increased gene dosage
Monosomy worse than trisomy since deleterious alleles often expressed (del mutations)
X chromosomes naturally aneuploid
Drosophila (♀XX ♂XO and XY)
X chromosome of male is hyperactivated
Mammals (♀XX ♂XY)
only one X active
Dosage compensation