Fine-Scale Signatures of Molecular Evolution Reconcile Models of Indel-Associated Mutation

Genomic structural alterations that vary within species, known as large copy number variants, represent an unanticipated and abundant source of genetic diversity that associates with variation in gene expression and susceptibility to disease. Even short insertions and deletions (indels) can exert im...

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Autores principales: Jovelin, Richard, Cutter, Asher D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673634/
https://www.ncbi.nlm.nih.gov/pubmed/23558593
http://dx.doi.org/10.1093/gbe/evt051
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author Jovelin, Richard
Cutter, Asher D.
author_facet Jovelin, Richard
Cutter, Asher D.
author_sort Jovelin, Richard
collection PubMed
description Genomic structural alterations that vary within species, known as large copy number variants, represent an unanticipated and abundant source of genetic diversity that associates with variation in gene expression and susceptibility to disease. Even short insertions and deletions (indels) can exert important effects on genomes by locally increasing the mutation rate, with multiple mechanisms proposed to account for this pattern. To better understand how indels promote genome evolution, we demonstrate that the single nucleotide mutation rate is elevated in the vicinity of indels, with a resolution of tens of base pairs, for the two closely related nematode species Caenorhabditis remanei and C. sp. 23. In addition to indels being clustered with single nucleotide polymorphisms and fixed differences, we also show that transversion mutations are enriched in sequences that flank indels and that many indels associate with sequence repeats. These observations are compatible with a model that reconciles previously proposed mechanisms of indel-associated mutagenesis, implicating repeat sequences as a common driver of indel errors, which then recruit error-prone polymerases during DNA repair, resulting in a locally elevated single nucleotide mutation rate. The striking influence of indel variants on the molecular evolution of flanking sequences strengthens the emerging general view that mutations can induce further mutations.
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spelling pubmed-36736342013-06-05 Fine-Scale Signatures of Molecular Evolution Reconcile Models of Indel-Associated Mutation Jovelin, Richard Cutter, Asher D. Genome Biol Evol Research Article Genomic structural alterations that vary within species, known as large copy number variants, represent an unanticipated and abundant source of genetic diversity that associates with variation in gene expression and susceptibility to disease. Even short insertions and deletions (indels) can exert important effects on genomes by locally increasing the mutation rate, with multiple mechanisms proposed to account for this pattern. To better understand how indels promote genome evolution, we demonstrate that the single nucleotide mutation rate is elevated in the vicinity of indels, with a resolution of tens of base pairs, for the two closely related nematode species Caenorhabditis remanei and C. sp. 23. In addition to indels being clustered with single nucleotide polymorphisms and fixed differences, we also show that transversion mutations are enriched in sequences that flank indels and that many indels associate with sequence repeats. These observations are compatible with a model that reconciles previously proposed mechanisms of indel-associated mutagenesis, implicating repeat sequences as a common driver of indel errors, which then recruit error-prone polymerases during DNA repair, resulting in a locally elevated single nucleotide mutation rate. The striking influence of indel variants on the molecular evolution of flanking sequences strengthens the emerging general view that mutations can induce further mutations. Oxford University Press 2013 2013-04-04 /pmc/articles/PMC3673634/ /pubmed/23558593 http://dx.doi.org/10.1093/gbe/evt051 Text en © The Author(s) 2013. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Research Article
Jovelin, Richard
Cutter, Asher D.
Fine-Scale Signatures of Molecular Evolution Reconcile Models of Indel-Associated Mutation
title Fine-Scale Signatures of Molecular Evolution Reconcile Models of Indel-Associated Mutation
title_full Fine-Scale Signatures of Molecular Evolution Reconcile Models of Indel-Associated Mutation
title_fullStr Fine-Scale Signatures of Molecular Evolution Reconcile Models of Indel-Associated Mutation
title_full_unstemmed Fine-Scale Signatures of Molecular Evolution Reconcile Models of Indel-Associated Mutation
title_short Fine-Scale Signatures of Molecular Evolution Reconcile Models of Indel-Associated Mutation
title_sort fine-scale signatures of molecular evolution reconcile models of indel-associated mutation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673634/
https://www.ncbi.nlm.nih.gov/pubmed/23558593
http://dx.doi.org/10.1093/gbe/evt051
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