The robustness of naturally and artificially selected nucleic acid secondary structures.
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.
Section of Integrative Biology, University of Texas at Austin, 1 University Station C0930, Austin, TX 78712, USA. ancel@mail.utexas.edu
Lauren Ancel
LA
Meyers
Jennifer F
JF
Lee
Matthew
M
Cowperthwaite
Andrew D
AD
Ellington
D001482:Base Composition; D003198:Computer Simulation; D030541:Databases, Genetic; D042822:Genomic Instability / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D009690:Nucleic Acid Conformation; D012313:RNA / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics*; D016337:RNA, Catalytic / Q000235:genetics; D012641:Selection, Genetic; D013816:Thermodynamics
D016337:RNA, Catalytic; D012313:RNA