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Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations

Mutations provide the raw material of evolution, and thus our ability to study evolution depends fundamentally on having precise measurements of mutational rates and patterns. We generate a data set for this purpose using (1) de novo mutations from mutation accumulation experiments and (2) extremely...

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Autores principales: Assaf, Zoe June, Tilk, Susanne, Park, Jane, Siegal, Mark L., Petrov, Dmitri A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741049/
https://www.ncbi.nlm.nih.gov/pubmed/29079675
http://dx.doi.org/10.1101/gr.219956.116
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author Assaf, Zoe June
Tilk, Susanne
Park, Jane
Siegal, Mark L.
Petrov, Dmitri A.
author_facet Assaf, Zoe June
Tilk, Susanne
Park, Jane
Siegal, Mark L.
Petrov, Dmitri A.
author_sort Assaf, Zoe June
collection PubMed
description Mutations provide the raw material of evolution, and thus our ability to study evolution depends fundamentally on having precise measurements of mutational rates and patterns. We generate a data set for this purpose using (1) de novo mutations from mutation accumulation experiments and (2) extremely rare polymorphisms from natural populations. The first, mutation accumulation (MA) lines are the product of maintaining flies in tiny populations for many generations, therefore rendering natural selection ineffective and allowing new mutations to accrue in the genome. The second, rare genetic variation from natural populations allows the study of mutation because extremely rare polymorphisms are relatively unaffected by the filter of natural selection. We use both methods in Drosophila melanogaster, first generating our own novel data set of sequenced MA lines and performing a meta-analysis of all published MA mutations (∼2000 events) and then identifying a high quality set of ∼70,000 extremely rare (≤0.1%) polymorphisms that are fully validated with resequencing. We use these data sets to precisely measure mutational rates and patterns. Highlights of our results include: a high rate of multinucleotide mutation events at both short (∼5 bp) and long (∼1 kb) genomic distances, showing that mutation drives GC content lower in already GC-poor regions, and using our precise context-dependent mutation rates to predict long-term evolutionary patterns at synonymous sites. We also show that de novo mutations from independent MA experiments display similar patterns of single nucleotide mutation and well match the patterns of mutation found in natural populations.
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spelling pubmed-57410492018-06-01 Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations Assaf, Zoe June Tilk, Susanne Park, Jane Siegal, Mark L. Petrov, Dmitri A. Genome Res Research Mutations provide the raw material of evolution, and thus our ability to study evolution depends fundamentally on having precise measurements of mutational rates and patterns. We generate a data set for this purpose using (1) de novo mutations from mutation accumulation experiments and (2) extremely rare polymorphisms from natural populations. The first, mutation accumulation (MA) lines are the product of maintaining flies in tiny populations for many generations, therefore rendering natural selection ineffective and allowing new mutations to accrue in the genome. The second, rare genetic variation from natural populations allows the study of mutation because extremely rare polymorphisms are relatively unaffected by the filter of natural selection. We use both methods in Drosophila melanogaster, first generating our own novel data set of sequenced MA lines and performing a meta-analysis of all published MA mutations (∼2000 events) and then identifying a high quality set of ∼70,000 extremely rare (≤0.1%) polymorphisms that are fully validated with resequencing. We use these data sets to precisely measure mutational rates and patterns. Highlights of our results include: a high rate of multinucleotide mutation events at both short (∼5 bp) and long (∼1 kb) genomic distances, showing that mutation drives GC content lower in already GC-poor regions, and using our precise context-dependent mutation rates to predict long-term evolutionary patterns at synonymous sites. We also show that de novo mutations from independent MA experiments display similar patterns of single nucleotide mutation and well match the patterns of mutation found in natural populations. Cold Spring Harbor Laboratory Press 2017-12 /pmc/articles/PMC5741049/ /pubmed/29079675 http://dx.doi.org/10.1101/gr.219956.116 Text en © 2017 Assaf et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Assaf, Zoe June
Tilk, Susanne
Park, Jane
Siegal, Mark L.
Petrov, Dmitri A.
Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations
title Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations
title_full Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations
title_fullStr Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations
title_full_unstemmed Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations
title_short Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations
title_sort deep sequencing of natural and experimental populations of drosophila melanogaster reveals biases in the spectrum of new mutations
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741049/
https://www.ncbi.nlm.nih.gov/pubmed/29079675
http://dx.doi.org/10.1101/gr.219956.116
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