The promiscuity and degeneracy of ten unique RNA base-pairing rules can determine the success of adaptive RNA evolution
- 1Department of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland
- 2Swiss Institute of Bioinformatics, Lausanne, Switzerland
- 3CRG (Barcelona Collaboratorium for Modelling and Predictive Biology), Barcelona, Spain
Abstract
The topography of fitness landscapes strongly influences the outcome of Darwinian evolution. This topography in turn is determined by the effects of genotypic changes on phenotypes, such as the structure and function of biomolecules like proteins and RNA. Thus, understanding the evolution of biomolecules requires an understanding of the relationship between genotype and phenotype. Here, we study how this relationship is influenced by the fundamental biochemical rules that determine which RNA bases can form base-pairs in RNA secondary structure. To this end, we computationally study the secondary structure genotype-phenotype maps of RNA molecules using all ten possible different such RNA base-pairing rules. We simulate adaptive evolution on fitness landscapes in which an RNA’s fitness is defined by its secondary structure. We find that the base-pairing rules strongly affect how likely an evolving population is to find the global peak of a fitness landscape. The base-pairing rule of most biological RNA molecules (A-U, G-C, G-U) is among the top three most favorable rules for adaptive evolution, in which over 80% of evolving populations find a landscape’s highest fitness peak. Simple characteristics of the genotype-phenotype map, such as the fraction of genotypes that constitute local peaks can help to predict how likely evolving populations are to find a landscape’s global fitness peak. These characteristics can in turn be explained by two elementary properties of base-pairing rules that we call promiscuity and degeneracy. Author summary: All living systems change and adapt according to the rules of Darwinian evolution. On the molecular scale, all of life is comprised of just a few types of biomolecules, RNA being one of them. The structure and function of these biomolecules is constrained by a limited set of building blocks and the rules that govern their interactions. In this study, we ask how the fundamental rules that govern RNA structure affect Darwinian evolution. We find that using alternative sets of building blocks with different interactions than those of biological RNA molecules can seriously hamper the effectiveness of Darwinian evolution. The interactions among biological RNA building blocks is among the most evolutionarily effective in facilitating Darwinian evolution.
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BibTeX
@article{goldbach2026promiscuity,
title = {{The promiscuity and degeneracy of ten unique RNA base-pairing rules can determine the success of adaptive RNA evolution}},
author = {Leander Goldbach and Nora S. Martin and Andreas Wagner},
journal = {PLOS Computational Biology},
year = {2026},
month = nov,
doi = {10.1371/journal.pcbi.1014914},
url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014914},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The promiscuity and degeneracy of ten unique RNA base-pairing rules can determine the success of adaptive RNA evolution
AU - Leander Goldbach
AU - Nora S. Martin
AU - Andreas Wagner
PY - 2026
DA - 2026/11/02
JO - PLOS Computational Biology
DO - 10.1371/journal.pcbi.1014914
UR - https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014914
AB - The topography of fitness landscapes strongly influences the outcome of Darwinian evolution. This topography in turn is determined by the effects of genotypic changes on phenotypes, such as the structure and function of biomolecules like proteins and RNA. Thus, understanding the evolution of biomolecules requires an understanding of the relationship between genotype and phenotype. Here, we study how this relationship is influenced by the fundamental biochemical rules that determine which RNA bases can form base-pairs in RNA secondary structure. To this end, we computationally study the secondary structure genotype-phenotype maps of RNA molecules using all ten possible different such RNA base-pairing rules. We simulate adaptive evolution on fitness landscapes in which an RNA’s fitness is defined by its secondary structure. We find that the base-pairing rules strongly affect how likely an evolving population is to find the global peak of a fitness landscape. The base-pairing rule of most biological RNA molecules (A-U, G-C, G-U) is among the top three most favorable rules for adaptive evolution, in which over 80% of evolving populations find a landscape’s highest fitness peak. Simple characteristics of the genotype-phenotype map, such as the fraction of genotypes that constitute local peaks can help to predict how likely evolving populations are to find a landscape’s global fitness peak. These characteristics can in turn be explained by two elementary properties of base-pairing rules that we call promiscuity and degeneracy. Author summary: All living systems change and adapt according to the rules of Darwinian evolution. On the molecular scale, all of life is comprised of just a few types of biomolecules, RNA being one of them. The structure and function of these biomolecules is constrained by a limited set of building blocks and the rules that govern their interactions. In this study, we ask how the fundamental rules that govern RNA structure affect Darwinian evolution. We find that using alternative sets of building blocks with different interactions than those of biological RNA molecules can seriously hamper the effectiveness of Darwinian evolution. The interactions among biological RNA building blocks is among the most evolutionarily effective in facilitating Darwinian evolution.
SN - 1553-7358
ER -