SB201 Discussion Questions – Stochastic Patterning Of the three models for coordination of gene expression that the authors suggest, does any seem to be favored by the current body of evidence available (perhaps from other similar studies)? Preferable from the standpoint of robustness to variation? What is responsible for determining the frequency of Ss allelic expression, and how stereotyped is this frequency? In terms of other examples of stochastic patterning, how conserved is this sort of mechanism? The cis-regulatory element from the ss(prot-null1) allele up-regulates the expression frequency of the ss(low freq1) allele, yet in another experiment the ss(low freq1) allele seemingly down-regulates the expression frequency from ss(wild-type). Might this alternatively be interpreted as the up-regulation of the ss(low-freq1) allele to a degree that simply fails to fully match the expression level with homozygous wild-type? The paper compares the fly eye’s mechanisms to the human eye’s, what might be the most important reason we see this difference in regulation? While stochastic mechanisms are cost-effective, are there any other processes that are even lower cost? How many step-processes are necessary for stochastic processes to remain controlled? Under what conditions might more constraints be necessary or unnecessary? Are there existing molecular examples of the models for coordination of expression proposed by the authors? Not necessarily in coordination of expression events – but are there other known instances in which the described “independent decision/tug of war”, “imposition of decision”, and “contemporaneous compilation of activating and repressing inputs” occur? Could position within the developing eye disc affect this process? Do you think the enhancer/silencers could respond differently depending on relation to the morphogenetic furrow… do we expect the enhancer/silencers for each allele to respond in the same way? Which model(s) for random expression seem most likely to be true? Is one of the models more commonly found than the others in systems utilizing stochastic expression? Can we think of any other models? What might allow one allele to “win” over the other in the tug of war mechanism, or to be designated the “decider” rather than the naïve allele? How could you test their various models for interchromosomal communication? If this goes wrong (i.e. something like the trunc mutant that they used), what is the effect on vision? Is it detrimental enough to cause a lot of evolutionary pressure for flies?