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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