The RNA folding map, understood as the relationship between sequences and secondary structures or shapes, 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).
The concept of a neutral network is particularly illuminating. Neutral networks loosen the requirements on the mutation rate for selection to remain effective. What needs to be preserved in a population is not a particular sequence, but rather a shape. This mandates a reformulation of the original (genotypic) error threshold in terms of a phenotypic error threshold confirming the intuition that more errors can be tolerated at higher degrees of neutrality.
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.
Submitted to Complexity.
Keywords: Immune system, design arguments, somatic mutation
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