SB201 Discussion Questions – GRNs: Garfield et al.

How generalizable do we think these findings about the importance of position in the
network are?

The authors mention that this species is known to have “extensive variation within
regulatory elements” within the wild population, without which this study wouldn’t be
possible. Do certain classes of organisms have more variation than others?

The animals bred for this experiment are coming from the natural population, so
presumably any variation in their skeletal morphology is not too detrimental to their ability
to feed/survive, or it wouldn’t still be present in the population. So are the range of skeletal
phenotypes that they see really that ecologically relevant?

What are the possible mechanisms for the change of level of buffering between early stage
and later stage? Does this model apply to other organisms?

Are there any other models for balancing robustness and evolvability?

In situations like a gene regulatory cascade, a little change in early gene expression normally
results in several-magnitude change in terminal gene. Why this is not the case in
morphological variance.
SB201 Discussion Questions – GRNs: Peter et al.

They list cell lineage geometry, cis-regulatory functioning, and signaling interactions as the
necessary inputs, are these three necessary and sufficient?

What major differences would there be in the model if they had not based their spatial
domains off that of sea urchin embryos? What effect does this have on the model’s
generality?

Is it actually surprising that stepwise time reproduces the dynamics described by the model
in experiments?

What outside factors might lead to the model’s discrepancies that resulted in having to
manually turn genes on/off to produce the experimental downstream effects observed?

For the regulatory output of different genes, is the “on” and “off” assumption okay to
make? Should the authors be accounting for things like tenability?

Similarly, the authors also assume that proteins only harbor two biochemical states – again
“on” and “off”. Does this not contradict what we know about proteins with differential
regulation based on many phosphorylation sites?

The authors claim that no finer temporal resolution is needed that 1 hr step times. For this
system, do you think this is a safe assumption to make?

In addition to the items mentioned above, the authors’ model fails to take into account
other variables such as co-factors, chromatin states, etc. Given that the model still
recapitulates experimental/expected results very well, is this telling us something about the
relative importance of these mechanisms used for tunability? Or, is this model simply
operating on a different scale such that those processes need not be considered?