• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jan 9, 1996; 93(1): 397–401.

Smoothness within ruggedness: the role of neutrality in adaptation.


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kimura M. Evolutionary rate at the molecular level. Nature. 1968 Feb 17;217(5129):624–626. [PubMed]
  • Pütz J, Puglisi JD, Florentz C, Giegé R. Identity elements for specific aminoacylation of yeast tRNA(Asp) by cognate aspartyl-tRNA synthetase. Science. 1991 Jun 21;252(5013):1696–1699. [PubMed]
  • Sassanfar M, Szostak JW. An RNA motif that binds ATP. Nature. 1993 Aug 5;364(6437):550–553. [PubMed]
  • Komiyama NH, Miyazaki G, Tame J, Nagai K. Transplanting a unique allosteric effect from crocodile into human haemoglobin. Nature. 1995 Jan 19;373(6511):244–246. [PubMed]
  • Zuker M, Stiegler P. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. 1981 Jan 10;9(1):133–148. [PMC free article] [PubMed]
  • Schuster P, Fontana W, Stadler PF, Hofacker IL. From sequences to shapes and back: a case study in RNA secondary structures. Proc Biol Sci. 1994 Mar 22;255(1344):279–284. [PubMed]
  • Bonhoeffer S, McCaskill JS, Stadler PF, Schuster P. RNA multi-structure landscapes. A study based on temperature dependent partition functions. Eur Biophys J. 1993;22(1):13–24. [PubMed]
  • Fontana W, Schnabl W, Schuster P. Physical aspects of evolutionary optimization and adaptation. Phys Rev A. 1989 Sep 15;40(6):3301–3321. [PubMed]
  • Eigen M. Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften. 1971 Oct;58(10):465–523. [PubMed]
  • Mills DR, Peterson RL, Spiegelman S. An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule. Proc Natl Acad Sci U S A. 1967 Jul;58(1):217–224. [PMC free article] [PubMed]
  • Levisohn R, Spiegelman S. Further extracellular Darwinian experiments with replicating RNA molecules: diverse variants isolated under different selective conditions. Proc Natl Acad Sci U S A. 1969 Jul;63(3):805–811. [PMC free article] [PubMed]
  • Joyce GF. Amplification, mutation and selection of catalytic RNA. Gene. 1989 Oct 15;82(1):83–87. [PubMed]
  • Robertson DL, Joyce GF. Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature. 1990 Mar 29;344(6265):467–468. [PubMed]
  • Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands. Nature. 1990 Aug 30;346(6287):818–822. [PubMed]
  • Beaudry AA, Joyce GF. Directed evolution of an RNA enzyme. Science. 1992 Jul 31;257(5070):635–641. [PubMed]
  • Berek C, Ziegner M. The maturation of the immune response. Immunol Today. 1993 Aug;14(8):400–404. [PubMed]
  • SNEATH PH. Some thoughts on bacterial classification. J Gen Microbiol. 1957 Aug;17(1):184–200. [PubMed]
  • Shapiro BA, Zhang KZ. Comparing multiple RNA secondary structures using tree comparisons. Comput Appl Biosci. 1990 Oct;6(4):309–318. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...