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From sequences to shapes and back: a case study in RNA secondary structures
P Schuster1, W Fontana, P F Stadler
1Institut für Molekulare Biotechnologie, Jena, Germany.
Proceedings. Biological Sciences
|March 22, 1994
Summary
RNA sequences can fold into a limited number of structures, with common structures easily accessible via mutations. This suggests RNA evolution readily finds functional molecules.
Area of Science:
- Molecular Biology
- Bioinformatics
- Evolutionary Biology
Background:
- RNA folding determines function, but the relationship between RNA sequence and structure is complex.
- The vast number of possible RNA sequences suggests a combinatorial challenge in finding functional structures.
Purpose of the Study:
- To investigate the relationship between RNA sequence space and secondary structure.
- To determine the accessibility of common RNA structures through sequence mutations.
- To explore the implications for RNA evolution and molecular evolution.
Main Methods:
- Utilized an inverse folding algorithm to analyze sequence-structure relationships.
- Examined the distribution and frequency of RNA secondary structures.
- Investigated the mutational pathways between sequences with identical structures.
Main Results:
- RNA structure frequencies follow a generalized Zipf's law, with few common and many rare structures.
- Sequences with the same structure are randomly distributed in sequence space.
- Common RNA structures are accessible from any sequence with a small number of mutations.
- Extensive neutral networks connect sequences that fold into identical structures.
Conclusions:
- Finding functional RNA structures through mutation and selection is more feasible than previously assumed.
- The interconnectedness of sequence space via neutral networks facilitates evolutionary exploration.
- Evolutionary processes are well-equipped to discover functional RNA structures, even those with sparse catalytic activity.