Switching States in Nature

jee suggested I post this in the forum for Rhiju. I think it’s my first posting:

Jieux: what is the maximum number of states found in nature? [5:05 PM]

Would also be curious what the average number is as well.


I don’t think we know the answer to your question. The main issue is that we have few experimental ways to decipher the # states that are relevant to an RNA’s function.

Most scientists try to assume the smallest number of states that fit their data, but usually the data collected on any particular RNA sequence is not that information-rich, and so folks use 2 or 3-state models when they describe their experiments.

But for an RNA message, or a viral genome, the number of states could be 100s, and they could all come into play during the functional cycle of the RNA. At some extremes (RNAs that splice themselves out of other RNAs, ribosomes that synthesize other proteins) there are clearly more than 3 states, but there aren’t really models that encompass these states and permit new predictions.

One of the main goals of our lab is develop experimental methods to dissect all of these states, if present, and figure out what they are doing… and I’m anticipating that it will be very helpful to have EteRNA players help analyze these data! As a start, we’ll be releasing puzzles soon on ‘designer’ switches that are going into yeast cells, and in parallel my lab will be collecting mutate-and-map data for a few designs that should help constrain the number of states at play.

Thank you for your quick reply to my inquiry. I would be curious if there would be a relationship between number of states and the total free energy of a molecule.

I don’t think there will be a correlation between total free energy and number of states, since I can make the total free energy arbitrarily large by adding in a super-long hairpin at any end.
However, there might be a correlation between number of states and the free energy difference between the lowest energy structure and the next lowest energy structure – I haven’t checked! This is the kind of thing we could quickly test in silico with some designs, and hopefully soon by experiment.