An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice
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 dissectio...
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doaj-3e7e931bf8674a47bc9d21c67150cb5f2021-05-05T17:39:39ZengeLife Sciences Publications LtdeLife2050-084X2019-06-01810.7554/eLife.42014An integrative genomic analysis of the Longshanks selection experiment for longer limbs in miceJoão PL Castro0Michelle N Yancoskie1Marta Marchini2Stefanie Belohlavy3Layla Hiramatsu4https://orcid.org/0000-0001-6298-6109Marek Kučka5William H Beluch6Ronald Naumann7Isabella Skuplik8John Cobb9https://orcid.org/0000-0002-1053-2604Nicholas H Barton10https://orcid.org/0000-0002-8548-5240Campbell Rolian11https://orcid.org/0000-0002-7242-342XYingguang Frank Chan12https://orcid.org/0000-0001-6292-9681Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, GermanyFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, GermanyUniversity of Calgary, Calgary, CanadaInstitute of Science and Technology (IST) Austria, Klosterneuburg, AustriaFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, GermanyFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, GermanyFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, GermanyMax Planck Institute for Molecular Cell Biology and Genetics, Dresden, GermanyUniversity of Calgary, Calgary, CanadaUniversity of Calgary, Calgary, CanadaInstitute of Science and Technology (IST) Austria, Klosterneuburg, AustriaUniversity of Calgary, Calgary, CanadaFriedrich Miescher Laboratory of the Max Planck Society, Tübingen, GermanyEvolutionary 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.https://elifesciences.org/articles/42014selection experimentquantitative geneticspopulation geneticsselective sweepslimb developmentenhancers |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
João PL Castro Michelle N Yancoskie Marta Marchini Stefanie Belohlavy Layla Hiramatsu Marek Kučka William H Beluch Ronald Naumann Isabella Skuplik John Cobb Nicholas H Barton Campbell Rolian Yingguang Frank Chan |
spellingShingle |
João PL Castro Michelle N Yancoskie Marta Marchini Stefanie Belohlavy Layla Hiramatsu Marek Kučka William H Beluch Ronald Naumann Isabella Skuplik John Cobb Nicholas H Barton Campbell Rolian Yingguang Frank Chan An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice eLife selection experiment quantitative genetics population genetics selective sweeps limb development enhancers |
author_facet |
João PL Castro Michelle N Yancoskie Marta Marchini Stefanie Belohlavy Layla Hiramatsu Marek Kučka William H Beluch Ronald Naumann Isabella Skuplik John Cobb Nicholas H Barton Campbell Rolian Yingguang Frank Chan |
author_sort |
João PL Castro |
title |
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice |
title_short |
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice |
title_full |
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice |
title_fullStr |
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice |
title_full_unstemmed |
An integrative genomic analysis of the Longshanks selection experiment for longer limbs in mice |
title_sort |
integrative genomic analysis of the longshanks selection experiment for longer limbs in mice |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2019-06-01 |
description |
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. |
topic |
selection experiment quantitative genetics population genetics selective sweeps limb development enhancers |
url |
https://elifesciences.org/articles/42014 |
work_keys_str_mv |
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