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Series GSE121564 Query DataSets for GSE121564
Status Public on Jul 09, 2019
Title An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice (4C-seq)
Organism Mus musculus
Experiment type Other
Summary Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicates. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci likely to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivating two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response.
Overall design Whole genome sequencing of the founding and generation 17 of three lines of mice (6 population samples in total). Statistical modelling of the selection response was performed in order to identify candidate regions responsible for the rapid increase in tibia length. One major locus found to show parallel selection response was Nkx3-2 on Chr5 of the mouse genome. Since no coding mutations were found that could be attributable as the target of selection, functional genomic techniques such as ATAC-Seq and 4C-Seq were performed to help identify relevant functional elements for further investigation and functional dissection. 4C-Seq was performed from fore- and hindlimb tissues as well as liver controls from the "viewpoint" of three enhancers (labelled as N1-N3) as identified by a combination of chromatin modification marks from the ENCODE project and ATAC-Seq signals of open chromatin. Proxmity ligation was performed on BglII sites, and religated amplicons from the chosen viewpoints were amplified for sequencing. Chimeric ligation products were interpreted as indicative of potential chromosome contacts.
Contributor(s) Castro JP, Yancoskie MN, Marchini M, Belohlavy S, Kučka M, Beluch WH, Naumann R, Skuplik I, Cobb J, Barton NH, Rolian C, Chan YF
Citation(s) 31169497
Submission date Oct 22, 2018
Last update date Jul 09, 2019
Contact name Yingguang Frank Chan
Phone 07071601888
Organization name Friedrich Miescher Laboratory
Street address Max-Planck-Ring 9
City Tübingen
ZIP/Postal code 72076
Country Germany
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (27)
GSM3439256 4C_Seq_Forelimb_Rep1_N1
GSM3439257 4C_Seq_Forelimb_Rep2_N1
GSM3439258 4C_Seq_Forelimb_Rep3_N1
This SubSeries is part of SuperSeries:
GSE121566 An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice
BioProject PRJNA497803
SRA SRP166279

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Supplementary file Size Download File type/resource
GSE121564_RAW.tar 236.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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