Molecular determinants and guided evolution of species-specific RNA editing

Nature. 2005 Mar 17;434(7031):409-13. doi: 10.1038/nature03364.


Most RNA editing systems are mechanistically diverse, informationally restorative, and scattershot in eukaryotic lineages. In contrast, genetic recoding by adenosine-to-inosine RNA editing seems common in animals; usually, altering highly conserved or invariant coding positions in proteins. Here I report striking variation between species in the recoding of synaptotagmin I (sytI). Fruitflies, mosquitoes and butterflies possess shared and species-specific sytI editing sites, all within a single exon. Honeybees, beetles and roaches do not edit sytI. The editing machinery is usually directed to modify particular adenosines by information stored in intron-mediated RNA structures. Combining comparative genomics of 34 species with mutational analysis reveals that complex, multi-domain, pre-mRNA structures solely determine species-appropriate RNA editing. One of these is a previously unreported long-range pseudoknot. I show that small changes to intronic sequences, far removed from an editing site, can transfer the species specificity of editing between RNA substrates. Taken together, these data support a phylogeny of sytI gene editing spanning more than 250 million years of hexapod evolution. The results also provide models for the genesis of RNA editing sites through the stepwise addition of structural domains, or by short walks through sequence space from ancestral structures.

Publication types

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

MeSH terms

  • Adenosine / genetics
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium-Binding Proteins / genetics*
  • Evolution, Molecular*
  • Exons / genetics
  • Genomics*
  • Inosine / genetics
  • Introns / genetics
  • Membrane Glycoproteins / genetics*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics*
  • Phylogeny
  • RNA Editing / genetics*
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • Species Specificity
  • Synaptotagmin I
  • Synaptotagmins
  • Time Factors


  • Calcium-Binding Proteins
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • RNA Precursors
  • Synaptotagmin I
  • Synaptotagmins
  • Inosine
  • Adenosine