Progressive loss of function in a limb enhancer during snake evolution
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
The evolution of body shape is thought to be tightly coupled to changes in regulatory sequences, but specific molecular events associated with major morphological transitions in vertebrates have remained elusive. We identified snake-specific sequence changes within an otherwise highly conserved long-range limb enhancer of Sonic hedgehog (Shh). Transgenic mouse reporter assays revealed that the in vivo activity pattern of the enhancer is conserved across a wide range of vertebrates, including fish, but not in snakes. Genomic substitution of the mouse enhancer with its human or fish ortholog results in normal limb development. In contrast, replacement with snake orthologs caused severe limb reduction. Synthetic restoration of a single transcription factor binding site lost in the snake lineage reinstated full in vivo function to the snake enhancer. Our results demonstrate changes in a regulatory sequence associated with a major body plan transition and highlight the role of enhancers in morphological evolution.
Date Issued
2016-10-20
Date Acceptance
2016-09-15
Citation
Cell, 2016, 167 (3), pp.633-642.e11
ISSN
0092-8674
Start Page
633
End Page
642.e11
Journal / Book Title
Cell
Volume
167
Issue
3
Copyright Statement
© 2016 Elsevier Inc. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Subjects
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Notes
publisher: Elsevier articletitle: Progressive Loss of Function in a Limb Enhancer during Snake Evolution journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2016.09.028 content_type: article copyright: © 2016 Elsevier Inc.
Publication Status
Published
Date Publish Online
2016-10-20