skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Progressive Loss of Function in a Limb Enhancer during Snake Evolution

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. In this paper, 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.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1398431
DOE Contract Number:  
AC02-05CH11231
Resource Type:
Journal Article
Journal Name:
Cell
Additional Journal Information:
Journal Volume: 167; Journal Issue: 3; Journal ID: ISSN 0092-8674
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Kvon, Evgeny Z., Kamneva, Olga K., Melo, Uirá S., Barozzi, Iros, Osterwalder, Marco, Mannion, Brandon J., Tissières, Virginie, Pickle, Catherine S., Plajzer-Frick, Ingrid, Lee, Elizabeth A., Kato, Momoe, Garvin, Tyler H., Akiyama, Jennifer A., Afzal, Veena, Lopez-Rios, Javier, Rubin, Edward M., Dickel, Diane E., Pennacchio, Len A., and Visel, Axel. Progressive Loss of Function in a Limb Enhancer during Snake Evolution. United States: N. p., 2016. Web. doi:10.1016/j.cell.2016.09.028.
Kvon, Evgeny Z., Kamneva, Olga K., Melo, Uirá S., Barozzi, Iros, Osterwalder, Marco, Mannion, Brandon J., Tissières, Virginie, Pickle, Catherine S., Plajzer-Frick, Ingrid, Lee, Elizabeth A., Kato, Momoe, Garvin, Tyler H., Akiyama, Jennifer A., Afzal, Veena, Lopez-Rios, Javier, Rubin, Edward M., Dickel, Diane E., Pennacchio, Len A., & Visel, Axel. Progressive Loss of Function in a Limb Enhancer during Snake Evolution. United States. https://doi.org/10.1016/j.cell.2016.09.028
Kvon, Evgeny Z., Kamneva, Olga K., Melo, Uirá S., Barozzi, Iros, Osterwalder, Marco, Mannion, Brandon J., Tissières, Virginie, Pickle, Catherine S., Plajzer-Frick, Ingrid, Lee, Elizabeth A., Kato, Momoe, Garvin, Tyler H., Akiyama, Jennifer A., Afzal, Veena, Lopez-Rios, Javier, Rubin, Edward M., Dickel, Diane E., Pennacchio, Len A., and Visel, Axel. 2016. "Progressive Loss of Function in a Limb Enhancer during Snake Evolution". United States. https://doi.org/10.1016/j.cell.2016.09.028.
@article{osti_1398431,
title = {Progressive Loss of Function in a Limb Enhancer during Snake Evolution},
author = {Kvon, Evgeny Z. and Kamneva, Olga K. and Melo, Uirá S. and Barozzi, Iros and Osterwalder, Marco and Mannion, Brandon J. and Tissières, Virginie and Pickle, Catherine S. and Plajzer-Frick, Ingrid and Lee, Elizabeth A. and Kato, Momoe and Garvin, Tyler H. and Akiyama, Jennifer A. and Afzal, Veena and Lopez-Rios, Javier and Rubin, Edward M. and Dickel, Diane E. and Pennacchio, Len A. and Visel, Axel},
abstractNote = {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. In this paper, 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.},
doi = {10.1016/j.cell.2016.09.028},
url = {https://www.osti.gov/biblio/1398431}, journal = {Cell},
issn = {0092-8674},
number = 3,
volume = 167,
place = {United States},
year = {Thu Oct 20 00:00:00 EDT 2016},
month = {Thu Oct 20 00:00:00 EDT 2016}
}