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TODO List
  • REF: energy fold is quite far from the conserved fold (Hofacker et al 2002 REF).
  • REF: recent advances show an increasingly expanding role for RNA in biology (REF)
  • REF: repertoires of RNAs have become larger (Hertel et al REF)
  • REF: 4% of DNA is functional RNA's



Accuracy and relevance of RNA landscape


So far we have focused on RNA structure as a paradigm for genotype-phenotype mapping, mainly because it is most (or only) computable mapping that we have a the moment. By looking at its high dimensional space we have seen that it is rugged, and that it has an extensive neutral network both at a local and global level, i.e. the more flat parts of the landscape. RNA is a good example to use since it is obviously an important biological molecule and has a computable mapping.

However, there are still problems with the minumum energy configuration. For example, in 16s RNA and 23s RNA molecules the minimum energy fold is quite far from the conserved fold (Hofacker et al 2002 REF). Most helices are there, but there are major differences in global basepairing. It appears that the folding is actually more local than in the minimum energy as we compute it.

So how can we improve this?
  • by recognizing the global-local mistake
  • study sequential folding
  • get more local oriented folding
  • get phylogenetic information to find out what is the most likely structure, i.e. most consistent folding over several species, energy contributions averaged over aligned sequences, compensatory mutations signal basepairing.

Another question we can ask is how important the RNA world is? How relevant is it?
  • recent advances show an increasingly expanding role for RNA in biology (REF)
  • mapping of functional RNAs in phyologenies shows that they expand during evolution (Bompfnevener et al REF?)
  • not really replaced by proteins as previously thought
  • in metazoa: more and more RNAs have been added during evolution, repertoires of RNAs have become larger (Hertel et al REF)
  • 4% of DNA is functional RNAs


Next: Multiple coding


References