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Fast free-energy-based neutral set size estimates for the RNA genotype-phenotype map.

Published version
Peer-reviewed

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Authors

Abstract

The genotype-phenotype (GP) map of RNA secondary structure links each RNA sequence to its corresponding secondary structure. Previous research has shown that the large-scale structural properties of GP maps, such as the size of neutral sets in genotype space, can influence evolutionary outcomes. In order to use neutral set sizes, efficient and accurate computational methods are needed to compute them. Here, we propose a new method, which is based on free energy estimates and is much faster than existing sample-based methods. Moreover, this approach can give insight into the reasons behind neutral set size variations, for example, why structures with fewer stacks tend to have larger neutral set sizes. In addition, we generalize neutral set size calculations from the previously studied many-to-one framework, where each sequence folds into a single energetically preferred structure, to a fuller many-to-many framework, where several low-energy structures are included. We find that structures with high neutral sets in one framework also tend to have large neutral sets in the other framework for a range of parameters and thus the choice of GP map does not fundamentally affect which structures have the largest neutral set sizes.

Description

Funder: Winton Programme for the Physics of Sustainability


Funder: Gates Cambridge Trust; Id: http://dx.doi.org/10.13039/501100005370

Keywords

Life Sciences–Physics interface, Research articles, RNA secondary structure, sequence–structure map, genotype–phenotype map, neutral set

Journal Title

J R Soc Interface

Conference Name

Journal ISSN

1742-5689
1742-5662

Volume Title

19

Publisher

The Royal Society
Sponsorship
Gatsby Charitable Foundation (PTAG/021)