1. LECTURE 21 LARGE-SCALE CHROMOSOME CHANGES I
revisit DNA repair
chapter 15
overview
chromosome number
chromosome structure
humans

2. GENERAL REVIEW
Friday December 8
9 am – 12 noon
WHI 105
be prepared to ask & answer questions

3. BIOLOGICAL REPAIR
error-free, pre-/no replication, single strand damage
direct chemical reversal of damaged base e.g., photorepair of UV-induced T-dimer
base excision & replacement, DNA glycosylases
segment excision & replacement prokaryotes: exinuclease, DNA pol I, ligase eukaryotes: transcription-coupled “repairisome”
(b & c) complementary template strand used to restore sequence

4. BIOLOGICAL REPAIR
error-prone, during replication, single strand damage
SOS repair
error-prone DNA pols

5. BIOLOGICAL REPAIR error-free, post-replication, single strand damage
mismatch repair in prokaryotes
complementary template strand used to restore sequence

6. BIOLOGICAL REPAIR error-free, post-replication, double strand damage
homologous recombination
complementary sister chromatid used to restore sequence

7. BIOLOGICAL REPAIR error-prone, no replication, double strand damage
non-homologous end joining… trim & patch

8. BIOLOGICAL REPAIR error-prone, post-replication, double strand damage
crossing-over… gene conversion, either with or without associated strand exchange

9. MEIOTIC CROSSING-OVER
initiated by double-stranded chromosome breakage
between 2 homologous non-sister chromatids
no gain or loss of genetic material
2 steps
double stranded breakage
heteroduplex DNA formed, derived from non-sister chromatids on homologous chromosomes

10. MEIOTIC CROSSING-OVER
double-stranded break model of crossing-over

11. MEIOTIC CROSSING-OVER
double-stranded break model of crossing-over

12. MEIOTIC CROSSING-OVER
double-stranded break model of crossing-over

13. MEIOTIC CROSSING-OVER
evidence first from aberrant ratios observed in fungi
aberrant asci have > 4 copies of on genotype
extra copies changed through gene conversion
5:3 ratio from non-identical sister spores in meiosis
with heteroduplex... A a

14. MEIOTIC CROSSING-OVER
evidence first from aberrant ratios observed in fungi
aberrant asci have > 4 copies of on genotype
extra copies changed through gene conversion
5:3 ratio from non-identical sister spores in meiosis
with heteroduplex not repaired A a

15. MEIOTIC CROSSING-OVER
evidence first from aberrant ratios observed in fungi
aberrant asci have > 4 copies of on genotype
extra copies changed through gene conversion
6:2 ratio from non-identical sister spores in meiosis
with heteroduplex repaired A a

16. MEIOTIC CROSSING-OVER
how to think about this problem...
ROTATE PERSPECTIVE
BRANCH MIGRATION
conversion
“horizontal breakage”
BREAKS

17. MEIOTIC CROSSING-OVER
how to think about this problem...
BRANCH MIGRATION
ROTATE PERSPECTIVE
BREAKS
recombination
“vertical breakage”

18. MEIOTIC CROSSING-OVER
how to think about this problem...
BRANCH MIGRATION
thanks to Bill Engels, Univ. Wisconsin

19. MEIOTIC CROSSING-OVER
how to think about this problem...
ROTATE PERSECTIVE
thanks to Bill Engels, Univ. Wisconsin

20. OVERVIEW 2 general questions to consider... is the genome complete?
is the genome balanced?

21. OVERVIEW
3 classes of chromosome change   

22. CHANGES IN CHROMOSOME NUMBER
2 classes of changes in chromosome sets
euploids / aberrant euploidy: whole sets
aneuploids / aneuploidy: partial sets

23. CHANGES IN CHROMOSOME NUMBER
“ploidy” terminology
monoploid (n): 1 chromosome set (abnormal)
haploid (n): 1 chromosome set (normal)
euploid (>1n): >1 chromosome set
polyploid (>2n): >2 chromosome sets
triploid, tetraploid, pentaploid, hexaploid...

24. CHANGES IN CHROMOSOME NUMBER
monoploids (n)
some insects are haplo-diploid (e.g. bees)
males develop from unfertilized eggs
their gametes form by mitosis
not found in most animals
due to recessive mutations = genetic load
masked by wild-type alleles in diploids
surviving monoploids are sterile in most animals

25. CHANGES IN CHROMOSOME NUMBER
polyploids (>2n)
common in plants, important in plant evolution
even #s most common n > 12
duplicated chromosome sets  new species

26. CHANGES IN CHROMOSOME NUMBER
polyploids (>2n)
aberrant euploids are often larger than their diploid counterparts, e.g.:
tobacco leaf cells 
oysters 

27. CHANGES IN CHROMOSOME NUMBER
2 types of polyploids, multiple chromosome sets originating from different sources
autopolyploids:
1 species
chromosomes fully homologous
allopolyploids:
2 related species
chromosomes only partially homologous

28. CHANGES IN CHROMOSOME NUMBER
autopolyploids
diploid (2n)  tetraploid (4n)...
fusion of gametes: n + 2n  triploid (3n)
triploids (& all odd# n)  aneuploid gametes
1 or 2 chromosomes / each type  2° meiocyte

29. CHANGES IN CHROMOSOME NUMBER
autopolyploids
triploids  aneuploid gametes &  usually sterile
P  ½ for each chromosome type
as n , P (balanced gametes) ...e.g.:
if n  10, P (2n gamete)  (1/2)10  0.001

30. CHANGES IN CHROMOSOME NUMBER
autopolyploids
diploid (2n)  2 (spontaneous)  tetraploid (4n) or
diploid (2n) + colchicine (disrupt microtubules) 

31. CHANGES IN CHROMOSOME NUMBER
autopolyploids
tetraploids  diploid gametes &  usually viable
some trivalent / univalent combinations  aneuploid gametes & offspring

32. CHANGES IN CHROMOSOME NUMBER
autopolyploids
what are the genotypic & phenotypic probabilities in the progeny of a P cross A/A/A/a  A/A/A/a?
P gametes: P(A/A) = P(A/a) = ½, P(a/a) = 0
F1 genotypes: P(A/A/A/A) = (½)2 = ¼
P(A/A/A/a) = 2(½)2 = ½
P(A/A/a/a) = (½)2 = ¼
F1 phenotypes: all A
A/A/a/a?
A/a/a/a?

33. CHANGES IN CHROMOSOME NUMBER
allopolyploids
useful for agriculture... blend characteristics of 2 plants... 1st e.g.: cabbage + radish (both 2n = 18)
n + n gametes  sterile 2n diploid
sterile 2n diploid colchicine  fertile 4n = amphidiploid

34. CHANGES IN CHROMOSOME NUMBER
allopolyploids in nature
importance in production of new species

35. CHANGES IN CHROMOSOME NUMBER
allopolyploids synthesized in the laboratory
sometimes, n1 + n2 gametes  viable 2n hybrids
n1 + n2 gametes  sterile 2n hybrids + colchicine  viable 2n1 + 2n2 = 4n amphidiploid (double diploid)
fusion of 2n1 + 2n2 cells  4n tetraploid

36. CHANGES IN CHROMOSOME NUMBER
agriculture
diploids mask expression of recessive traits
monoploids express recessive traits; retain desirable, dispose of deleterious
monoploid culture  select  double chromosomes

37. CHANGES IN CHROMOSOME NUMBER
agriculture
diploids mask expression of recessive traits
monoploids express recessive traits; retain desirable, dispose of deleterious
monoploid culture  select  double chromosomes
can also use method with mutagenesis to generate new varieties with desirable traits, e.g.:
pesticide resistance
drought tollerance

38. CHANGES IN CHROMOSOME NUMBER
agriculture
autotriploids, e.g. bananas (3n = 33)
sterile, seeds nearly absent
autotetraploids, e.g. grapes
bigger
allopolyploids, e.g wheat, cotton, many others
DIPLOID TETRAPLOID

39. CHANGES IN CHROMOSOME NUMBER
polyploid animals
less common than in plants
sterility is the main barrier for this process
 polyploid animals are often parthenogenic
lower invertebrates, some crustaceans, fish, amphibians & reptiles
triploid & tetraploid Drosophila have been synthesized in the lab

40. CHANGES IN CHROMOSOME NUMBER
aneuploidy
+ or - 1 or 2 chromosomes
diploids
2n + 1  trisomic / trisomy
2n - 1  monosomic / monosomy
2n - 2  nullosomic / nullosomy
haploids
n + 1  disomic / disomy
sex chromosomes require specific notation, e.g., XXX, X0, XYY, etc

41. CHANGES IN CHROMOSOME NUMBER
aneuploidy
by nondisjuction = abnormal segregation
meiotic (2 ways)  whole organism affected
normal disjuction aided by crossing over
mitotic  mosaic patches affected

42. CHANGES IN CHROMOSOME NUMBER
aneuploidy
gene balance ~ gene dosage affects
gene products function in a balanced coctail
imbalance affects physiological pathways
important genes may be haplo- or triplo-abnormal
X-chromosome expression level same in males & females because of dosage compensation
fruit flies - males have hyperactive X
mammals - females have only 1 transcriptionally active X