---
_id: '6713'
abstract:
- lang: eng
  text: 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.
article_number: e42014
article_processing_charge: No
author:
- first_name: João Pl
  full_name: Castro, João Pl
  last_name: Castro
- first_name: Michelle N.
  full_name: Yancoskie, Michelle N.
  last_name: Yancoskie
- first_name: Marta
  full_name: Marchini, Marta
  last_name: Marchini
- first_name: Stefanie
  full_name: Belohlavy, Stefanie
  id: 43FE426A-F248-11E8-B48F-1D18A9856A87
  last_name: Belohlavy
  orcid: 0000-0002-9849-498X
- first_name: Layla
  full_name: Hiramatsu, Layla
  last_name: Hiramatsu
- first_name: Marek
  full_name: Kučka, Marek
  last_name: Kučka
- first_name: William H.
  full_name: Beluch, William H.
  last_name: Beluch
- first_name: Ronald
  full_name: Naumann, Ronald
  last_name: Naumann
- first_name: Isabella
  full_name: Skuplik, Isabella
  last_name: Skuplik
- first_name: John
  full_name: Cobb, John
  last_name: Cobb
- first_name: Nicholas H
  full_name: Barton, Nicholas H
  id: 4880FE40-F248-11E8-B48F-1D18A9856A87
  last_name: Barton
  orcid: 0000-0002-8548-5240
- first_name: Campbell
  full_name: Rolian, Campbell
  last_name: Rolian
- first_name: Yingguang Frank
  full_name: Chan, Yingguang Frank
  last_name: Chan
citation:
  ama: Castro JP, Yancoskie MN, Marchini M, et al. An integrative genomic analysis
    of the Longshanks selection experiment for longer limbs in mice. <i>eLife</i>.
    2019;8. doi:<a href="https://doi.org/10.7554/eLife.42014">10.7554/eLife.42014</a>
  apa: Castro, J. P., Yancoskie, M. N., Marchini, M., Belohlavy, S., Hiramatsu, L.,
    Kučka, M., … Chan, Y. F. (2019). An integrative genomic analysis of the Longshanks
    selection experiment for longer limbs in mice. <i>ELife</i>. eLife Sciences Publications.
    <a href="https://doi.org/10.7554/eLife.42014">https://doi.org/10.7554/eLife.42014</a>
  chicago: Castro, João Pl, Michelle N. Yancoskie, Marta Marchini, Stefanie Belohlavy,
    Layla Hiramatsu, Marek Kučka, William H. Beluch, et al. “An Integrative Genomic
    Analysis of the Longshanks Selection Experiment for Longer Limbs in Mice.” <i>ELife</i>.
    eLife Sciences Publications, 2019. <a href="https://doi.org/10.7554/eLife.42014">https://doi.org/10.7554/eLife.42014</a>.
  ieee: J. P. Castro <i>et al.</i>, “An integrative genomic analysis of the Longshanks
    selection experiment for longer limbs in mice,” <i>eLife</i>, vol. 8. eLife Sciences
    Publications, 2019.
  ista: Castro JP, Yancoskie MN, Marchini M, Belohlavy S, Hiramatsu L, Kučka M, Beluch
    WH, Naumann R, Skuplik I, Cobb J, Barton NH, Rolian C, Chan YF. 2019. An integrative
    genomic analysis of the Longshanks selection experiment for longer limbs in mice.
    eLife. 8, e42014.
  mla: Castro, João Pl, et al. “An Integrative Genomic Analysis of the Longshanks
    Selection Experiment for Longer Limbs in Mice.” <i>ELife</i>, vol. 8, e42014,
    eLife Sciences Publications, 2019, doi:<a href="https://doi.org/10.7554/eLife.42014">10.7554/eLife.42014</a>.
  short: J.P. Castro, M.N. Yancoskie, M. Marchini, S. Belohlavy, L. Hiramatsu, M.
    Kučka, W.H. Beluch, R. Naumann, I. Skuplik, J. Cobb, N.H. Barton, C. Rolian, Y.F.
    Chan, ELife 8 (2019).
date_created: 2019-07-28T21:59:17Z
date_published: 2019-06-06T00:00:00Z
date_updated: 2026-06-09T22:30:39Z
day: '06'
ddc:
- '576'
department:
- _id: NiBa
doi: 10.7554/eLife.42014
external_id:
  isi:
  - '000473588700001'
  pmid:
  - '31169497'
file:
- access_level: open_access
  checksum: fa0936fe58f0d9e3f8e75038570e5a17
  content_type: application/pdf
  creator: apreinsp
  date_created: 2019-07-29T07:41:18Z
  date_updated: 2020-07-14T12:47:38Z
  file_id: '6721'
  file_name: 2019_eLife_Castro.pdf
  file_size: 6748249
  relation: main_file
file_date_updated: 2020-07-14T12:47:38Z
has_accepted_license: '1'
intvolume: '         8'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  record:
  - id: '9804'
    relation: research_data
    status: public
  - id: '11388'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: An integrative genomic analysis of the Longshanks selection experiment for
  longer limbs in mice
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 8
year: '2019'
...