Transcript file

The role of imperfections in
biological systems
Jan 2013
Regulatory Genomics
Lecturer: Prof. Yitzhak Pilpel
What types of imperfections are
there?
• Mutations
• Transcription / translation errors (of what
type)
• Nois expression
• More?...
What could be the potential
benefits of imperfections?
How can we measure …
• Rate of transcription errors
• Rate of translation errors?
• Nois
Functionally useful
imperfections in transcription
What is hysteresis?
WT
MT
L
H
H
L
Hysteresis is the dependence of a system not only on its current
environment but also on its past environment.
The effect of error prone RNA
pol II
ly
“Look ahead” phenotypic error:
a potential means to obtain paired mutations
Challenge for the system: reward the organism
(fitness wise) for even the first mutation.
Solution: the allele will spread due to sporadic
phenotypic mutations
Bacterial persistence
A single cell investigation reveals the
basis of persistence
Balaban et al. Science 2004
A stochastic switch maintains persistent
cells in the population
The broader relevance in
persistence
• In response to antibiotics
• In response to viral attack
• In cancer cells responding to a chemotherapy
• In the natural environmental warfare
among (microbial) species
A major medical concer
Can we use the notion to identify cells
that would escape chemo-therapy?
Bimodal expression of key proteins
predict survival upon drug treatment
Apply the same notion to
explain incomplete penetrance
Incomplete penetrance
• What is it?
• Why is it important/interesting?
• What could be the underling cause/basis
for it?
• How could knowing the basis be useful?
Pre-mutation diversity in a paralog
determines mutational fate
Pre-mutation: “anticipation”
Post-mutation: response
A theoretical model predicts
how backup filters noise
Kafri Pilpel PNAS 2006
A chaperon (Hsp90): acts as a
“Capacitor” of mutations