An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice
- Friedrich Miescher Laboratory of the Max Planck Society, Germany
- University of Calgary, Canada
- IST Austria, Austria
- Max Planck Institute for Cell Biology and Genetics, Germany
Abstract
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 tending 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.
Data availability
Sequencing data have been deposited in SRA (accession number SRP165718), GEO (accession numbers GSE121564, GSE121565 and GSE121566)Non-sequence data have been deposited at Dryad (doi:10.5061/dryad.0q2h6tk).Analytical code and additional notes have been deposited in the following repository: https://github.com/evolgenomics/LongshanksAdditional raw data and code are hosted via our institute's FTP servers at http://ftp.tuebingen.mpg.de/fml/ag-chan/Longshanks/
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An integrative genomic analysis of the Longshanks selection experiment for longer limbs in miceNCBI Sequence Read Archive, SRP165718.
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An integrative genomic analysis of the Longshanks selection experiment for longer limbs in miceNCBI Gene Expression Omnibus, GSE121564.
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An integrative genomic analysis of the Longshanks selection experiment for longer limbs in miceNCBI Gene Expression Omnibus, GSE121565.
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An integrative genomic analysis of the Longshanks selection experiment for longer limbs in miceNCBI Gene Expression Omnibus, GSE121566.
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Data from: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in miceDryad Digital Repository, doi:10.5061/dryad.0q2h6tk.
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Mouse Gene Expression DatabaseMouse Gene Expression Database.
Article and author information
Author details
Yingguang Frank Chan
Funding
Natural Sciences and Engineering Research Council of Canada (4181932)
- Campbell Rolian
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Magnus Nordborg, Austrian Academy of Sciences, Austria
Ethics
Animal experimentation: All experimental procedures described in this study have been approved by the applicable University institutional ethics committee for animal welfare at the University of Calgary (HSACC Protocols M08146 and AC13-0077); or local competent authority: Landesdirektion Sachsen, Germany, permit number 24-9168.11-9/2012-5.
Version history
- Received: September 14, 2018
- Accepted: May 19, 2019
- Accepted Manuscript published: June 6, 2019 (version 1)
- Version of Record published: July 2, 2019 (version 2)
Copyright
© 2019, Castro et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice
eLife 8:e42014.
https://doi.org/10.7554/eLife.42014
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