ArticleMolecular biology and evolution2022
Phenotype Bias Determines How Natural RNA Structures Occupy the Morphospace of All Possible Shapes.
Article in Molecular biology and evolution, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 52 citations in OpenAlex.
- Mechanisms of Phenotypic Evolution from Molecules to Organisms: Integrating Evolutionary Biochemistry and Evolutionary Developmental Biology.Annual review of ecology, evolution, and systematics · 2026Article
- Emergence Biases in Molecular Evolution.Genome biology and evolution · 2026Review
- Disease-related miRNA mutations are associated with mature miRNA secondary structure changes.Biophysical journal · 2025Article
- Bounding phenotype transition probabilities via conditional complexity.Journal of the Royal Society, Interface · 2025Article
- The structure of an ancient genotype-phenotype map shaped the functional evolution of a protein family.Nature ecology & evolution · 2025Article
- The structure of an ancient genotype-phenotype map shaped the functional evolution of a protein family.bioRxiv : the preprint server for biology · 2025Article
- Article
- Non-Poissonian Bursts in the Arrival of Phenotypic Variation Can Strongly Affect the Dynamics of Adaptation.Molecular biology and evolution · 2024Article
- Robust genetic codes enhance protein evolvability.PLoS biology · 2024Article
- Bias in the arrival of variation can dominate over natural selection in Richard Dawkins's biomorphs.PLoS computational biology · 2024Article
- The RNA-DNA world and the emergence of DNA-encoded heritable traits.RNA biology · 2024Article
- The Boltzmann distributions of molecular structures predict likely changes through random mutations.Biophysical journal · 2023Article
- The non-deterministic genotype-phenotype map of RNA secondary structure.Journal of the Royal Society, Interface · 2023Article
- Maximum mutational robustness in genotype-phenotype maps follows a self-similar blancmange-like curve.Journal of the Royal Society, Interface · 2023Article
- Mutation bias and the predictability of evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Random and Natural Non-Coding RNA Have Similar Structural Motif Patterns but Differ in Bulge, Loop, and Bond Counts.Life (Basel, Switzerland) · 2023Article
- Predicting phenotype transition probabilities via conditional algorithmic probability approximations.Journal of the Royal Society, Interface · 2022Article
- On the incongruence of genotype-phenotype and fitness landscapes.PLoS computational biology · 2022Article
- The Effect of Environment on the Evolution and Proliferation of Protocells of Increasing Complexity.Life (Basel, Switzerland) · 2022Article
- Reply to Ocklenburg and Mundorf: The interplay of developmental bias and natural selection.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Morphospaces-representations of phenotypic characteristics-are often populated unevenly, leaving large parts unoccupied. Such patterns are typically ascribed to contingency, or else to natural selection disfavoring certain parts of the morphospace. The extent to which developmental bias, the tendency of certain phenotypes to preferentially appear as potential variation, also explains these patterns is hotly debated. Here we demonstrate quantitatively that developmental bias is the primary explanation for the occupation of the morphospace of RNA secondary structure (SS) shapes. Upon random mutations, some RNA SS shapes (the frequent ones) are much more likely to appear than others. By using the RNAshapes method to define coarse-grained SS classes, we can directly compare the frequencies that noncoding RNA SS shapes appear in the RNAcentral database to frequencies obtained upon a random sampling of sequences. We show that: 1) only the most frequent structures appear in nature; the vast majority of possible structures in the morphospace have not yet been explored; 2) remarkably small numbers of random sequences are needed to produce all the RNA SS shapes found in nature so far; and 3) perhaps most surprisingly, the natural frequencies are accurately predicted, over several orders of magnitude in variation, by the likelihood that structures appear upon a uniform random sampling of sequences. The ultimate cause of these patterns is not natural selection, but rather a strong phenotype bias in the RNA genotype-phenotype map, a type of developmental bias or "findability constraint," which limits evolutionary dynamics to a hugely reduced subset of structures that are easy to "find."
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