  The relationship between sequences and secondary structures or shapes in RNA
exhibits robust statistical properties summarized by three notions: (1) the
notion of a typical shape (that among all sequences of fixed length certain
shapes are realized much more frequently than others), (2) the notion of shape
space covering (that all typical shapes are realized in a small neighborhood of
any random sequence), and (3) the notion of a neutral network (that sequences
folding into the same typical shape form networks that percolate through
sequence space). Neutral networks loosen the requirements on the mutation rate
for selection to remain effective. The original (genotypic) error threshold has
to be reformulated in terms of a phenotypic error threshold. With regard to
adaptation, neutrality has two seemingly contradictory effects: It acts as a
buffer against mutations ensuring that a phenotype is preserved. Yet it is
deeply enabling, because it permits evolutionary change to occur by allowing
the sequence context to vary silently until a single point mutation can become
phenotypically consequential. Neutrality also influences predictability of
adaptive trajectories in seemingly contradictory ways. On the one hand it
increases the uncertainty of their genotypic trace. At the same time neutrality
structures the access from one shape to another, thereby inducing a topology
among RNA shapes which permits a distinction between continuous and
discontinuous shape transformations. To the extent that adaptive trajectories
must undergo such transformations, their phenotypic trace becomes more
predictable.
