Journal of Molecular Evolution

, Volume 58, Issue 6, pp 681–691 | Cite as

The Robustness of Naturally and Artificially Selected Nucleic Acid Secondary Structures

  • Lauren Ancel MeyersEmail author
  • Jennifer F. Lee
  • Matthew Cowperthwaite
  • Andrew D. Ellington


Thermodynamic stability and mutational robustness of secondary structure are critical to the function and evolutionary longevity of RNA molecules. We hypothesize that natural and artificial selection for functional molecules favors the formation of structures that are stable to both thermal and mutational perturbation. There is little direct evidence, however, that functional RNA molecules have been selected for their stability. Here we use thermodynamic secondary structure prediction algorithms to compare the thermal and mutational robustness of over 1000 naturally and artificially evolved molecules. Although we find evidence for the evolution of both types of stability in both sets of molecules, the naturally evolved functional RNA molecules were significantly more stable than those selected in vitro, and artificially evolved catalysts (ribozymes) were more stable than artificially evolved binding species (aptamers). The thermostability of RNA molecules bred in the laboratory is probably not constrained by a lack of suitable variation in the sequence pool but, rather, by intrinsic biases in the selection process.


RNA Secondary structure Thermostability Mutational robustness Aptamer Ribozyme In vitro selection 



The authors thank Walter Fontana and Rob Knight for technical advice and Kourosh Salehi-Ashtiani and Jack Szostak at Mass General Hospital for providing selected ribozyme sequences. This work was supported in part by the Santa Fe Institute and grants from the NSF (Grant DEB-0303636) to L.A.M., grants from the NSF (Grant EIA-0218447) and the NIH–NIBIB (Grant 8R01EB002043) to A.D.E., and NSF-IGERT fellowships in computational phylogenetics to J.F.L and M.C.


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Lauren Ancel Meyers
    • 1
    • 2
    • 3
    Email author
  • Jennifer F. Lee
    • 2
  • Matthew Cowperthwaite
    • 2
  • Andrew D. Ellington
    • 2
  1. 1.Section of Integrative BiologyUniversity of Texas at AustinAustinUSA
  2. 2.Institute for Cellular and Molecular BiologyUniversity of Texas at AustinAustinUSA
  3. 3.Santa Fe Institute (External Faculty)Santa FeUSA

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