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Extra base hits: Widespread empirical support for instantaneous multiple-nucleotide changes

Despite many attempts to introduce evolutionary models that permit substitutions to instantly alter more than one nucleotide in a codon, the prevailing wisdom remains that such changes are rare and generally negligible or are reflective of non-biological artifacts, such as alignment errors. Codon mo...

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Autores principales: Lucaci, Alexander G., Wisotsky, Sadie R., Shank, Stephen D., Weaver, Steven, Kosakovsky Pond, Sergei L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954308/
https://www.ncbi.nlm.nih.gov/pubmed/33711070
http://dx.doi.org/10.1371/journal.pone.0248337
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author Lucaci, Alexander G.
Wisotsky, Sadie R.
Shank, Stephen D.
Weaver, Steven
Kosakovsky Pond, Sergei L.
author_facet Lucaci, Alexander G.
Wisotsky, Sadie R.
Shank, Stephen D.
Weaver, Steven
Kosakovsky Pond, Sergei L.
author_sort Lucaci, Alexander G.
collection PubMed
description Despite many attempts to introduce evolutionary models that permit substitutions to instantly alter more than one nucleotide in a codon, the prevailing wisdom remains that such changes are rare and generally negligible or are reflective of non-biological artifacts, such as alignment errors. Codon models continue to posit that only single nucleotide change have non-zero rates. Here, we develop and test a simple hierarchy of codon-substitution models with non-zero evolutionary rates for only one-nucleotide (1H), one- and two-nucleotide (2H), or any (3H) codon substitutions. Using over 42, 000 empirical alignments, we find widespread statistical support for multiple hits: 61% of alignments prefer models with 2H allowed, and 23%—with 3H allowed. Analyses of simulated data suggest that these results are not likely to be due to simple artifacts such as model misspecification or alignment errors. Further modeling reveals that synonymous codon island jumping among codons encoding serine, especially along short branches, contributes significantly to this 3H signal. While serine codons were prominently involved in multiple-hit substitutions, there were other common exchanges contributing to better model fit. It appears that a small subset of sites in most alignments have unusual evolutionary dynamics not well explained by existing model formalisms, and that commonly estimated quantities, such as dN/dS ratios may be biased by model misspecification. Our findings highlight the need for continued evaluation of assumptions underlying workhorse evolutionary models and subsequent evolutionary inference techniques. We provide a software implementation for evolutionary biologists to assess the potential impact of extra base hits in their data in the HyPhy package and in the Datamonkey.org server.
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spelling pubmed-79543082021-03-22 Extra base hits: Widespread empirical support for instantaneous multiple-nucleotide changes Lucaci, Alexander G. Wisotsky, Sadie R. Shank, Stephen D. Weaver, Steven Kosakovsky Pond, Sergei L. PLoS One Research Article Despite many attempts to introduce evolutionary models that permit substitutions to instantly alter more than one nucleotide in a codon, the prevailing wisdom remains that such changes are rare and generally negligible or are reflective of non-biological artifacts, such as alignment errors. Codon models continue to posit that only single nucleotide change have non-zero rates. Here, we develop and test a simple hierarchy of codon-substitution models with non-zero evolutionary rates for only one-nucleotide (1H), one- and two-nucleotide (2H), or any (3H) codon substitutions. Using over 42, 000 empirical alignments, we find widespread statistical support for multiple hits: 61% of alignments prefer models with 2H allowed, and 23%—with 3H allowed. Analyses of simulated data suggest that these results are not likely to be due to simple artifacts such as model misspecification or alignment errors. Further modeling reveals that synonymous codon island jumping among codons encoding serine, especially along short branches, contributes significantly to this 3H signal. While serine codons were prominently involved in multiple-hit substitutions, there were other common exchanges contributing to better model fit. It appears that a small subset of sites in most alignments have unusual evolutionary dynamics not well explained by existing model formalisms, and that commonly estimated quantities, such as dN/dS ratios may be biased by model misspecification. Our findings highlight the need for continued evaluation of assumptions underlying workhorse evolutionary models and subsequent evolutionary inference techniques. We provide a software implementation for evolutionary biologists to assess the potential impact of extra base hits in their data in the HyPhy package and in the Datamonkey.org server. Public Library of Science 2021-03-12 /pmc/articles/PMC7954308/ /pubmed/33711070 http://dx.doi.org/10.1371/journal.pone.0248337 Text en © 2021 Lucaci et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lucaci, Alexander G.
Wisotsky, Sadie R.
Shank, Stephen D.
Weaver, Steven
Kosakovsky Pond, Sergei L.
Extra base hits: Widespread empirical support for instantaneous multiple-nucleotide changes
title Extra base hits: Widespread empirical support for instantaneous multiple-nucleotide changes
title_full Extra base hits: Widespread empirical support for instantaneous multiple-nucleotide changes
title_fullStr Extra base hits: Widespread empirical support for instantaneous multiple-nucleotide changes
title_full_unstemmed Extra base hits: Widespread empirical support for instantaneous multiple-nucleotide changes
title_short Extra base hits: Widespread empirical support for instantaneous multiple-nucleotide changes
title_sort extra base hits: widespread empirical support for instantaneous multiple-nucleotide changes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954308/
https://www.ncbi.nlm.nih.gov/pubmed/33711070
http://dx.doi.org/10.1371/journal.pone.0248337
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