Natural and artificial RNAs occupy the same restricted region of sequence space

Ryan Kennedy, Manuel E. Lladser, Zhiyuan Wu, Chen Zhang, Michael Yarus, Hans De Sterck, Rob Knight

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

Different chemical and mutational processes within genomes give rise to sequences with different compositions and perhaps different capacities for evolution. The evolution of functional RNAs may occur on a "neutral network" in which sequences with any given function can easily mutate to sequences with any other. This neutral network hypothesis is more likely if there is a particular region of composition that contains sequences that are functional in general, and if many different functions are possible within this preferred region of composition. We show that sequence preferences in active sites recovered by in vitro selection combine with biophysical folding rules to support the neutral network hypothesis. These simple active-site specifications and folding preferences obtained by artificial selection experiments recapture the previously observed purine bias and specific spread along the GC axis of naturally occurring aptamers and ribozymes isolated from organisms, although other types of RNAs, such as miRNA precursors and spliceosomal RNAs, that act primarily through complementarity to other amino acids do not share these preferences. These universal evolved sequence features are therefore intrinsic in RNA molecules that bind small-molecule targets or catalyze reactions. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish
Pages (from-to)280-289
Number of pages10
JournalRna-A Publication of the Rna Society
Volume16
Issue number2
DOIs
Publication statusPublished - Feb 2010
Externally publishedYes

Keywords

  • In vitro selection
  • Nucleotide composition
  • SELEX
  • Self-organization

Cite this