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Insertions and deletions in the RNA sequence–structure map

Genotype–phenotype maps link genetic changes to their fitness effect and are thus an essential component of evolutionary models. The map between RNA sequences and their secondary structures is a key example and has applications in functional RNA evolution. For this map, the structural effect of subs...

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Detalles Bibliográficos
Autores principales: Martin, Nora S., Ahnert, Sebastian E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492174/
https://www.ncbi.nlm.nih.gov/pubmed/34610259
http://dx.doi.org/10.1098/rsif.2021.0380
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author Martin, Nora S.
Ahnert, Sebastian E.
author_facet Martin, Nora S.
Ahnert, Sebastian E.
author_sort Martin, Nora S.
collection PubMed
description Genotype–phenotype maps link genetic changes to their fitness effect and are thus an essential component of evolutionary models. The map between RNA sequences and their secondary structures is a key example and has applications in functional RNA evolution. For this map, the structural effect of substitutions is well understood, but models usually assume a constant sequence length and do not consider insertions or deletions. Here, we expand the sequence–structure map to include single nucleotide insertions and deletions by using the RNAshapes concept. To quantify the structural effect of insertions and deletions, we generalize existing definitions for robustness and non-neutral mutation probabilities. We find striking similarities between substitutions, deletions and insertions: robustness to substitutions is correlated with robustness to insertions and, for most structures, to deletions. In addition, frequent structural changes after substitutions also tend to be common for insertions and deletions. This is consistent with the connection between energetically suboptimal folds and possible structural transitions. The similarities observed hold both for genotypic and phenotypic robustness and mutation probabilities, i.e. for individual sequences and for averages over sequences with the same structure. Our results could have implications for the rate of neutral and non-neutral evolution.
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spelling pubmed-84921742021-11-03 Insertions and deletions in the RNA sequence–structure map Martin, Nora S. Ahnert, Sebastian E. J R Soc Interface Life Sciences–Physics interface Genotype–phenotype maps link genetic changes to their fitness effect and are thus an essential component of evolutionary models. The map between RNA sequences and their secondary structures is a key example and has applications in functional RNA evolution. For this map, the structural effect of substitutions is well understood, but models usually assume a constant sequence length and do not consider insertions or deletions. Here, we expand the sequence–structure map to include single nucleotide insertions and deletions by using the RNAshapes concept. To quantify the structural effect of insertions and deletions, we generalize existing definitions for robustness and non-neutral mutation probabilities. We find striking similarities between substitutions, deletions and insertions: robustness to substitutions is correlated with robustness to insertions and, for most structures, to deletions. In addition, frequent structural changes after substitutions also tend to be common for insertions and deletions. This is consistent with the connection between energetically suboptimal folds and possible structural transitions. The similarities observed hold both for genotypic and phenotypic robustness and mutation probabilities, i.e. for individual sequences and for averages over sequences with the same structure. Our results could have implications for the rate of neutral and non-neutral evolution. The Royal Society 2021-10-06 /pmc/articles/PMC8492174/ /pubmed/34610259 http://dx.doi.org/10.1098/rsif.2021.0380 Text en © 2021 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Life Sciences–Physics interface
Martin, Nora S.
Ahnert, Sebastian E.
Insertions and deletions in the RNA sequence–structure map
title Insertions and deletions in the RNA sequence–structure map
title_full Insertions and deletions in the RNA sequence–structure map
title_fullStr Insertions and deletions in the RNA sequence–structure map
title_full_unstemmed Insertions and deletions in the RNA sequence–structure map
title_short Insertions and deletions in the RNA sequence–structure map
title_sort insertions and deletions in the rna sequence–structure map
topic Life Sciences–Physics interface
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492174/
https://www.ncbi.nlm.nih.gov/pubmed/34610259
http://dx.doi.org/10.1098/rsif.2021.0380
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