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

Zoe June Assaf, Susanne Tilk, Jane Park, Mark Siegal, Dmitri A. Petrov

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1988-2000
Number of pages13
JournalGenome Research
Volume27
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

High-Throughput Nucleotide Sequencing
Drosophila melanogaster
Mutation
Population
Genetic Selection
Mutation Rate
Base Composition
Diptera
Meta-Analysis
Nucleotides
Mutation Accumulation
Genome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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; Petrov, Dmitri A.

In: Genome Research, Vol. 27, No. 12, 01.12.2017, p. 1988-2000.

Research output: Contribution to journalArticle

Assaf, Zoe June ; Tilk, Susanne ; Park, Jane ; Siegal, Mark ; Petrov, Dmitri A. / Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations. In: Genome Research. 2017 ; Vol. 27, No. 12. pp. 1988-2000.
@article{eb0c69e4f0254286a91c178fe036d943,
title = "Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations",
abstract = "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.",
author = "Assaf, {Zoe June} and Susanne Tilk and Jane Park and Mark Siegal and Petrov, {Dmitri A.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1101/gr.219956.116",
language = "English (US)",
volume = "27",
pages = "1988--2000",
journal = "Genome Research",
issn = "1088-9051",
publisher = "Cold Spring Harbor Laboratory Press",
number = "12",

}

TY - JOUR

T1 - Deep sequencing of natural and experimental populations of Drosophila melanogaster reveals biases in the spectrum of new mutations

AU - Assaf, Zoe June

AU - Tilk, Susanne

AU - Park, Jane

AU - Siegal, Mark

AU - Petrov, Dmitri A.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85037673804&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037673804&partnerID=8YFLogxK

U2 - 10.1101/gr.219956.116

DO - 10.1101/gr.219956.116

M3 - Article

C2 - 29079675

AN - SCOPUS:85037673804

VL - 27

SP - 1988

EP - 2000

JO - Genome Research

JF - Genome Research

SN - 1088-9051

IS - 12

ER -