How do organisms

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How do organisms stay the same? (canalization)
How do they change? (assimilation)
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Courtesy of Syozo Osawa JT Biohistory, Osaka
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Mimulus lewisii
Mimulus cardinalis
courtesy of Doug Schemske
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• Hsp90 buffers polymorphisms
• accumulate, sort recombine

• remain silent

• Environmental stress reveals them
• diverted to other proteins

• targets exquisitely sensitive
• Increase in Hsp90 outpaced by need

Together capacitor for evolutionary change
Mutations, drugs, environment stress
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How could such a system evolve? Hitchhike on
another mechanism
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Cell proliferation
G1 progression
Activation repression of gene expression
Translation initiation
MAP- kinase pathways
NO production
apoptosis
using many co-factors
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Kathy Borkovich
Debbie Nathan
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v-Src
Gal

accumulation
activity
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c-src
v-abl
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Suzanne Rutherford
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No!
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population before selection
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selected stock
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Why Arabidopsis?

• Profoundly different lifestyle
• sessile
• self-fertilizing
• developmentally plastic

• Great genetic model system
• small genome
• genetically divergent
• ecotypes
• recombinant inbred lines

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Holly Oakley Andrew Evans
Todd Sangster
Christine Queitsch
entire U of C Arabidopsis group!
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Col
Ler
Normal seedlings
GdA treated
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RI lines
X
F1 cross of different accessions Progeny selfed
to near homozygoisty
.
.
.
etc.
Line 1
Line 2
Line 3
Line 5
Line 4
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RNAi Vector
nptII
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Advantageous phenotypes?
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Hsp90 buffering How does stress effect
it? Creates hopeful monsters Cleanses the
gene pool ______ Enormous range of effects Many
types of variation?
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How many other ways do protein folding
mechanism affect such processes?
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The recombination of isolated genomes Crosses
between different strains Hybrid
vigor? Developmental instability?
X
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COL
LER
F1
DMSO
2 µM Geld
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Have these mechanisms helped shape evolution? Ca
n we make use of them ourselves?
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Improving Crops Without Transgenics?
Cross Two Divergent Crop Strains
X
Self-Cross Progeny
Hsp90 Levels Not Reduced
Reduced Hsp90 Levels
Hidden Genetic Variation Not Revealed
Hidden Genetic Variation Revealed
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Heat shock proteins and cancer
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Multi-step tumorigenesis a somatic evolution at
the cellular level
Fearon-Vogelstein colorectal cancer model
APC
K-ras
p53
SMAD2
SMAD4 DCC
Late adenoma
Normal epithelium
Early adenoma
Intermediate adenoma
carcinoma
Low-grade
High-grade
Normal tissue
Mutations Natural selection
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Malignancy is the result of alterations in
multiple cellular functions
1signal transduction 2cell cycle
control 3apoptosis
Hahn WC, Weinberg RA. Nat Rev Cancer.
20022(5)331-41.
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Heat shock proteins and cancers
Elevated HSP90 expression high in many human
cancers.
HSP90 stabilizes several oncoproteins e.g.
BCR-ABL, mutant p53
Specific HSP90 inhibitors(geldanamycin and
radicicol) promote the degradation of
oncoproteins and reduce tumor cell growth.
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THANKS!!
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THANKS, THANKS, and once again THANKS!
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COL
LER
F1
DMSO
2 µM Geld
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Heterozygous advantage under conditions
of moderate heat treatment
Parents
Crosses
Col
Col X Ler
Ler X Col
Ler
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Heterozygous advantage with moderate heat
treatment
Parents
Crosses
Col
Col X Ler
Ler X Col
Ler
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F1 progeny displays hybrid vigor under stress
without GdA
2 µM GdA
Ler parent
F1 progeny
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Quantitative analysis of hypocotyl
elongation 1) continuous trait 2) phenotypic
plasticity
Ler seedlings
light-grown
dark-grown
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GdA affects genetic variability of hypocotyl dark
response
CVG
 
h2
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QTL map of hypocotyl elongation with and without
GdA
GdA-specific QTL accounts for 3.8 mm and 12
variation.
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Variability in Hsp90RNAi Seedlings
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