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/
-
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
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.
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
-
- 4,176
- views
-
- 506
- downloads
-
- 60
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
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)
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice
eLife 8:e42014.
https://doi.org/10.7554/eLife.42014
Further reading
-
- Developmental Biology
- Neuroscience
In a developing nervous system, axonal arbors often undergo complex rearrangements before neural circuits attain their final innervation topology. In the lateral line sensory system of the zebrafish, developing sensory axons reorganize their terminal arborization patterns to establish precise neural microcircuits around the mechanosensory hair cells. However, a quantitative understanding of the changes in the sensory arbor morphology and the regulators behind the microcircuit assembly remain enigmatic. Here, we report that Semaphorin7A (Sema7A) acts as an important mediator of these processes. Utilizing a semi-automated three-dimensional neurite tracing methodology and computational techniques, we have identified and quantitatively analyzed distinct topological features that shape the network in wild-type and Sema7A loss-of-function mutants. In contrast to those of wild-type animals, the sensory axons in Sema7A mutants display aberrant arborizations with disorganized network topology and diminished contacts to hair cells. Moreover, ectopic expression of a secreted form of Sema7A by non-hair cells induces chemotropic guidance of sensory axons. Our findings propose that Sema7A likely functions both as a juxtracrine and as a secreted cue to pattern neural circuitry during sensory organ development.
-
- Chromosomes and Gene Expression
- Developmental Biology
Most teleost fishes exhibit a biphasic life history with a larval oceanic phase that is transformed into morphologically and physiologically different demersal, benthic, or pelagic juveniles. This process of transformation is characterized by a myriad of hormone-induced changes, during the often abrupt transition between larval and juvenile phases called metamorphosis. Thyroid hormones (TH) are known to be instrumental in triggering and coordinating this transformation but other hormonal systems such as corticoids, might be also involved as it is the case in amphibians. In order to investigate the potential involvement of these two hormonal pathways in marine fish post-embryonic development, we used the Malabar grouper (Epinephelus malabaricus) as a model system. We assembled a chromosome-scale genome sequence and conducted a transcriptomic analysis of nine larval developmental stages. We studied the expression patterns of genes involved in TH and corticoid pathways, as well as four biological processes known to be regulated by TH in other teleost species: ossification, pigmentation, visual perception, and metabolism. Surprisingly, we observed an activation of many of the same pathways involved in metamorphosis also at an early stage of the larval development, suggesting an additional implication of these pathways in the formation of early larval features. Overall, our data brings new evidence to the controversial interplay between corticoids and thyroid hormones during metamorphosis as well as, surprisingly, during the early larval development. Further experiments will be needed to investigate the precise role of both pathways during these two distinct periods and whether an early activation of both corticoid and TH pathways occurs in other teleost species.
