Commit 7d08e631 authored by Jerome Waldispuhl's avatar Jerome Waldispuhl
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tmp ref 2

parent 00da7cec
......@@ -183,15 +183,15 @@ My main criticism regards the ``distinct region of the sequence landscape enrich
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The discussion in the ms is confusing at several points because different lengths are mixed to discuss what is typical and what is not. In the absence of energetic considerations, the abundance of any structural motif converges to a Gaussian distribution for sufficiently long sequences (50 is already sufficiently long), and therefore typical shapes exist and can be defined. Check for instance Nebel, M.E., 2002. Combinatorial properties of RNA secondary structures. J. Comp. Biol. 9, 541?573 or Poznanovi?, S., Heitsch, C.E., 2014. Asymptotic distribution of motifs in a stochastic context-free grammar model of RNA folding. J. Math. Biol. 69, 1743?1772. In the light of those results the main question is: in which sense do structures in the "distinct region" differ from typical structures at those lengths? Can be those differences, if present at all, be ascribed to selection for low-energy folds? How are those results related to the apparent lack of structural selection identified by other authors (their ref. [18]), where most abundant structures seem to be the ones found in non-coding RNA databases? This main criticism takes different forms along the ms and in the light of a number of statements and interpretations, as follows.}
\methodstag
We agree with the reviewer that if the sampling was random then those results would hold. But as discussed previously it is not random but instead a weighted sampling.
We address each remark individually in the following. Nonetheless, we acknowledge that the term ``distinct region'' could have be unfortunate or ambiguous. When we speak of a region, it does not imply that it is a connected network or dense region of sequences. In fact, we noted on page 9 of our manuscript that the sequence entropy of mutants with stable multi-branched structures is high, and thus suggested that these sequences are randomly distributed.\\
We used the term ``distinct region'' to describe a set of sequences occurring at a specific GC content, but we acknowledge that this term was unnecessarily confusing.
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Page 1. "Non-coding RNAs acquire functions through complex structures." What is the basis for this claim? Do viroids have complex structures?}
\hypothesistag While definition of complex structure is still vague, we argue that multiloops are one of the important and easily identifiable features.
The basis is how quickly and often they appear in consensus structure of RFAM families at short lengths, as shown in Fig.1.
Viroids by themselves are an interesting example which have different replication mechanisms depending of relatively subtle changes in structures (Structural differences within the loop E-motif imply alternative mechanisms of viroid processing, RNA 2007. 13: 824-834).
The basis is how quickly and often they appear in consensus structures of RFAM families at short lengths, as shown in Figure~1.
Viroids by themselves are an interesting example which have different replication mechanisms depending of relatively subtle changes in structures \cite{Owens:2007aa}.
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