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

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”

BIOLOGICAL REPAIR

(b & c) complementary template strand used to

restore sequence

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

BIOLOGICAL REPAIR

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...

MEIOTIC CROSSING-OVER

AAAAaaaa

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

MEIOTIC CROSSING-OVER

AAAaaaaa

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

MEIOTIC CROSSING-OVER

AAaaaaaa

how to think about this problem...

MEIOTIC CROSSING-OVER

BRANCH MIGRATION ROTATE PERSPECTIVE

BREAKS conversion

“horizontal breakage”

MEIOTIC CROSSING-OVER

BRANCH MIGRATION ROTATE PERSPECTIVE

BREAKS

how to think about this problem...

recombination

“vertical breakage”

MEIOTIC CROSSING-OVER

BRANCH MIGRATIONthanks to Bill Engels, Univ. Wisconsin

how to think about this problem...

MEIOTIC CROSSING-OVER

ROTATE PERSECTIVEthanks to Bill Engels, Univ. Wisconsin

how to think about this problem...

2 general questions to consider... is the genome complete?

is the genome balanced?

OVERVIEW

3 classes of chromosome change

OVERVIEW

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

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?

autopolyploids

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