Smoothness within ruggedness: the role of neutrality in adaptation

Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):397-401. doi: 10.1073/pnas.93.1.397.


RNA secondary structure folding algorithms predict the existence of connected networks of RNA sequences with identical structure. On such networks, evolving populations split into subpopulations, which diffuse independently in sequence space. This demands a distinction between two mutation thresholds: one at which genotypic information is lost and one at which phenotypic information is lost. In between, diffusion enables the search of vast areas in genotype space while still preserving the dominant phenotype. By this dynamic the success of phenotypic adaptation becomes much less sensitive to the initial conditions in genotype space.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Biological*
  • Base Sequence
  • Biological Evolution
  • Genotype
  • Mutation
  • Nucleic Acid Conformation*
  • Phenotype
  • RNA / genetics*
  • Selection, Genetic*


  • RNA