An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice
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/
-
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in miceNCBI Sequence Read Archive, SRP165718.
-
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in miceNCBI Gene Expression Omnibus, GSE121564.
-
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in miceNCBI Gene Expression Omnibus, GSE121565.
-
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in miceNCBI Gene Expression Omnibus, GSE121566.
-
Data from: An integrative genomic analysis of the Longshanks selection experiment for longer limbs in miceDryad Digital Repository, doi:10.5061/dryad.0q2h6tk.
-
Mouse Gene Expression DatabaseMouse Gene Expression Database.
Article and author information
Author details
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.
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.
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.
Metrics
-
- 4,285
- views
-
- 514
- downloads
-
- 63
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Developmental Biology
Human autonomic neuronal cell models are emerging as tools for modeling diseases such as cardiac arrhythmias. In this systematic review, we compared 33 articles applying 14 different protocols to generate sympathetic neurons and 3 different procedures to produce parasympathetic neurons. All methods involved the differentiation of human pluripotent stem cells, and none employed permanent or reversible cell immortalization. Almost all protocols were reproduced in multiple pluripotent stem cell lines, and over half showed evidence of neural firing capacity. Common limitations in the field are a lack of three-dimensional models and models that include multiple cell types. Sympathetic neuron differentiation protocols largely mirrored embryonic development, with the notable absence of migration, axon extension, and target-specificity cues. Parasympathetic neuron differentiation protocols may be improved by including several embryonic cues promoting cell survival, cell maturation, or ion channel expression. Moreover, additional markers to define parasympathetic neurons in vitro may support the validity of these protocols. Nonetheless, four sympathetic neuron differentiation protocols and one parasympathetic neuron differentiation protocol reported more than two-thirds of cells expressing autonomic neuron markers. Altogether, these protocols promise to open new research avenues of human autonomic neuron development and disease modeling.
-
- Cell Biology
- Developmental Biology
A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.