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Int J Biol Sci 2017; 13(9):1138-1151. doi:10.7150/ijbs.19436

Research Paper

Effect of Population Size and Mutation Rate on the Evolution of RNA Sequences on an Adaptive Landscape Determined by RNA Folding

Ali R. Vahdati1, 2, Kathleen Sprouffske1, 2, Andreas Wagner1, 2, 3✉

1. Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland;
2. The Swiss Institute of Bioinformatics, Lausanne, Switzerland;
3. The Santa Fe Institute, Santa Fe, USA.


The dynamics of populations evolving on an adaptive landscape depends on multiple factors, including the structure of the landscape, the rate of mutations, and effective population size. Existing theoretical work often makes ad hoc and simplifying assumptions about landscape structure, whereas experimental work can vary important parameters only to a limited extent. We here overcome some of these limitations by simulating the adaptive evolution of RNA molecules, whose fitness is determined by the thermodynamics of RNA secondary structure folding. We study the influence of mutation rates and population sizes on final mean population fitness, on the substitution rates of mutations, and on population diversity. We show that evolutionary dynamics cannot be understood as a function of mutation rate µ, population size N, or population mutation rate alone. For example, at a given mutation rate, clonal interference prevents the fixation of beneficial mutations as population size increases, but larger populations still arrive at a higher mean fitness. In addition, at the highest population mutation rates we study, mean final fitness increases with population size, because small populations are driven to low fitness by the relatively higher incidence of mutations they experience. Our observations show that mutation rate and population size can interact in complex ways to influence the adaptive dynamics of a population on a biophysically motivated fitness landscape.

Keywords: population size, rate of adaptation, fitness landscape, RNA secondary structure.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
How to cite this article:
Vahdati AR, Sprouffske K, Wagner A. Effect of Population Size and Mutation Rate on the Evolution of RNA Sequences on an Adaptive Landscape Determined by RNA Folding. Int J Biol Sci 2017; 13(9):1138-1151. doi:10.7150/ijbs.19436. Available from