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Human Molecular Genetics Advance Access published online on May 10, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl123
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© The Author 2006. Published by Oxford University Press. All rights reserved
Received May 2, 2006
Accepted May 3, 2006

Article

Sonic Hedgehog, a key development gene, experienced intensified molecular evolution in primates

Steve Dorus 1, Jeffrey R. Anderson 2, Eric J. Vallender 1, Sandra L. Gilbert 2, Li Zhang 2, Leona G. Chemnick 3, Oliver A. Ryder 3, Weimin Li 2, and Bruce T. Lahn 2 *

1 Howard Hughes Medical Institute, Department of Human Genetics, Chicago, Illinois 60637, USA; Committee on Genetics, University of Chicago, Chicago, Illinois 60637, USA
2 Howard Hughes Medical Institute, Department of Human Genetics, Chicago, Illinois 60637, USA
3 Center for Reproduction of Endangered Species, Zoological Society of San Diego, California 92112

* To whom correspondence should be addressed.
Bruce T. Lahn, E-mail: blahn{at}bsd.uchicago.edu


  Abstract

Sonic Hedgehog (SHH) is one of the most intensively studied genes in developmental biology. It is a highly conserved gene, found in species as diverse as arthropods and mammals. The mammalian SHH encodes a signaling molecule that plays a central role in developmental patterning, especially of the nervous system and the skeletal system. Here, we show that the molecular evolution of SHH is markedly accelerated in primates relative to other mammals. We further show that within primates, the acceleration is most prominent along the lineage leading to humans. Finally, we show that the acceleration in the lineage leading to humans is coupled with signatures of adaptive evolution. In particular, the lineage leading to humans is characterized by a rampant and statistically highly nonrandom gain of serines and threonines, residues that are potential substrates of posttranslational modifications. This suggests that SHH might have evolved more complex posttranslational regulation in the lineage leading to humans. Collectively, these findings implicate SHH as a potential contributor to the evolution of primate- or human-specific morphological traits in the nervous and/or skeletal systems, and provide the impetus for additional studies aimed at identifying the primate- or human-specific functions of this key development gene.


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