Download GENETICS – BIO 300

LECTURE 21
LARGE-SCALE CHROMOSOME CHANGES I
revisit DNA repair
chapter 15
overview
chromosome number
chromosome structure
humans
GENERAL REVIEW
 Friday December 8
 9 am – 12 noon
 WHI 105
 be prepared to ask
& answer questions
BIOLOGICAL REPAIR
 error-free, pre-/no replication, single strand damage
(a) direct chemical reversal of damaged base
e.g., photorepair of UV-induced T-dimer
(b) base excision & replacement, DNA glycosylases
(c) segment excision & replacement
prokaryotes: exinuclease, DNA pol I, ligase
eukaryotes: transcription-coupled “repairisome”
(b & c) complementary template strand used to
restore sequence
BIOLOGICAL REPAIR
 error-prone, during replication, single strand damage
 SOS repair
 error-prone DNA pols
BIOLOGICAL REPAIR
 error-free, post-replication, single strand damage
 mismatch repair in
prokaryotes
 complementary template
strand used to restore
sequence
BIOLOGICAL REPAIR
 error-free, post-replication, double strand damage
 homologous
recombination
 complementary
sister chromatid
used to restore
sequence
BIOLOGICAL REPAIR
 error-prone, no replication, double strand damage
 non-homologous end joining… trim & patch
BIOLOGICAL REPAIR
 error-prone, post-replication, double strand damage
 crossing-over… gene conversion, either with or
without associated strand exchange
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
MEIOTIC CROSSING-OVER
 double-stranded break model of crossing-over
MEIOTIC CROSSING-OVER
 double-stranded break model of crossing-over
MEIOTIC CROSSING-OVER
 double-stranded break model of crossing-over
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
A
A
a
a
a
a
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
A
a
a
a
a
a
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
a
a
a
a
a
a
MEIOTIC CROSSING-OVER
 how to think about this problem...
BRANCH MIGRATION
 conversion
 “horizontal
breakage”
ROTATE PERSPECTIVE
BREAKS
MEIOTIC CROSSING-OVER
 how to think about this problem...
BRANCH MIGRATION
 recombination
 “vertical
breakage”
ROTATE PERSPECTIVE
BREAKS
MEIOTIC CROSSING-OVER
 how to think about this problem...
BRANCH MIGRATION
thanks to Bill Engels, Univ. Wisconsin
MEIOTIC CROSSING-OVER
 how to think about this problem...
ROTATE PERSECTIVE
thanks to Bill Engels, Univ. Wisconsin
OVERVIEW
 2 general questions to consider...
 is the genome complete?
 is the genome balanced?
OVERVIEW
 3 classes of chromosome change



CHANGES IN CHROMOSOME NUMBER
 2 classes of changes in chromosome sets
 euploids / aberrant euploidy: whole sets
 aneuploids / aneuploidy: partial sets
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...
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
CHANGES IN CHROMOSOME NUMBER
 polyploids (>2n)
 common in plants, important in plant evolution
 even #s most
common n > 12
 duplicated
chromosome sets
 new species
CHANGES IN CHROMOSOME NUMBER
 polyploids (>2n)
 aberrant euploids are
often larger than their
diploid counterparts, e.g.:
 tobacco leaf cells 
 oysters 
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
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
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
CHANGES IN CHROMOSOME NUMBER
 autopolyploids
 diploid (2n)  2 (spontaneous)  tetraploid (4n) or
 diploid (2n) + colchicine (disrupt microtubules) 
CHANGES IN CHROMOSOME NUMBER
 autopolyploids
 tetraploids  diploid gametes &  usually viable
 some trivalent / univalent combinations 
aneuploid gametes & offspring
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?
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 = 36
amphidiploid
CHANGES IN CHROMOSOME NUMBER
 allopolyploids in nature
 importance in production of new species
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
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
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
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
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
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
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
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