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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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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. |
format | Online Article Text |
id | pubmed-7954308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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