Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines.
The Drosophila melanogaster Genetic Reference Panel (DGRP) is a community resource of 205 sequenced inbred lines, derived to improve our understanding of the effects of naturally occurring genetic variation on molecular and organismal phenotypes. We used an integrated genotyping strategy to identify 4,853,802 single nucleotide polymorphisms (SNPs) and 1,296,080 non-SNP variants. Our molecular population genomic analyses show higher deletion than insertion mutation rates and stronger purifying selection on deletions. Weaker selection on insertions than deletions is consistent with our observed distribution of genome size determined by flow cytometry, which is skewed toward larger genomes. Insertion/deletion and single nucleotide polymorphisms are positively correlated with each other and with local recombination, suggesting that their nonrandom distributions are due to hitchhiking and background selection. Our cytogenetic analysis identified 16 polymorphic inversions in the DGRP. Common inverted and standard karyotypes are genetically divergent and account for most of the variation in relatedness among the DGRP lines. Intriguingly, variation in genome size and many quantitative traits are significantly associated with inversions. Approximately 50% of the DGRP lines are infected with Wolbachia, and four lines have germline insertions of Wolbachia sequences, but effects of Wolbachia infection on quantitative traits are rarely significant. The DGRP complements ongoing efforts to functionally annotate the Drosophila genome. Indeed, 15% of all D. melanogaster genes segregate for potentially damaged proteins in the DGRP, and genome-wide analyses of quantitative traits identify novel candidate genes. The DGRP lines, sequence data, genotypes, quality scores, phenotypes, and analysis and visualization tools are publicly available.
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
Wen
W
Huang
Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;
Andreas
A
Massouras
Center for Education in Liberal Arts and Sciences, Osaka University, Osaka-fu, 560-0043 Japan;
Yutaka
Y
Inoue
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
Jason
J
Peiffer
Genomics, Bioinformatics and Evolution Group, Institut de Biotecnologia i de Biomedicina (IBB), Department of Genetics and Microbiology, Campus Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
Miquel
M
Ràmia
Department of Entomology, Texas A&M University, College Station, Texas 77843, USA;
Aaron M
AM
Tarone
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
Lavanya
L
Turlapati
Genome Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany;
Thomas
T
Zichner
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Dianhui
D
Zhu
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
Richard F
RF
Lyman
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
Michael M
MM
Magwire
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Kerstin
K
Blankenburg
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
Mary Anna
MA
Carbone
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Kyle
K
Chang
Department of Entomology, Texas A&M University, College Station, Texas 77843, USA;
Lisa L
LL
Ellis
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Sonia
S
Fernandez
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Yi
Y
Han
Virginia Tech Virginia Bioinformatics Institute and Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia 24061, USA.
Gareth
G
Highnam
Department of Entomology, Texas A&M University, College Station, Texas 77843, USA;
Carl E
CE
Hjelmen
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
John R
JR
Jack
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Mehwish
M
Javaid
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Joy
J
Jayaseelan
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Divya
D
Kalra
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Sandy
S
Lee
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Lora
L
Lewis
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Mala
M
Munidasa
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Fiona
F
Ongeri
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Shohba
S
Patel
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Lora
L
Perales
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Agapito
A
Perez
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
LingLing
L
Pu
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
Stephanie M
SM
Rollmann
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Robert
R
Ruth
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Nehad
N
Saada
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Crystal
C
Warner
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Aneisa
A
Williams
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Yuan-Qing
YQ
Wu
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
Akihiko
A
Yamamoto
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Yiqing
Y
Zhang
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Yiming
Y
Zhu
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
Robert R H
RR
Anholt
Genome Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany;
Jan O
JO
Korbel
Virginia Tech Virginia Bioinformatics Institute and Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia 24061, USA.
David
D
Mittelman
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Donna M
DM
Muzny
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Richard A
RA
Gibbs
Genomics, Bioinformatics and Evolution Group, Institut de Biotecnologia i de Biomedicina (IBB), Department of Genetics and Microbiology, Campus Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain;
Antonio
A
Barbadilla
Department of Entomology, Texas A&M University, College Station, Texas 77843, USA;
J Spencer
JS
Johnston
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
Eric A
EA
Stone
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030 USA;
Stephen
S
Richards
Laboratory of Systems Biology and Genetics, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland;
Bart
B
Deplancke
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27595, USA;
Trudy F C
TF
Mackay
D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000382:microbiology; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D059646:Genome Size; D049750:Genome, Insect; D055106:Genome-Wide Association Study; D005838:Genotype; D060005:Genotyping Techniques; D059014:High-Throughput Nucleotide Sequencing; D054643:INDEL Mutation; D015810:Linkage Disequilibrium; D008297:Male; D058977:Molecular Sequence Annotation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D015203:Reproducibility of Results
D002843:Chromatin