Dorus Steve, Anderson Jeffrey R, Vallender Eric J, Gilbert Sandra L, Zhang Li, Chemnick Leona G, Ryder Oliver A, Li Weimin, Lahn Bruce T
Department of Human Genetics, Howard Hughes Medical Institute, USA.
Hum Mol Genet. 2006 Jul 1;15(13):2031-7. doi: 10.1093/hmg/ddl123. Epub 2006 May 10.
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 non-random gain of serines and threonines, residues that are potential substrates of post-translational modifications. This suggests that SHH might have evolved more complex post-translational 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.
音猬因子（SHH）是发育生物学中研究最为深入的基因之一。它是一个高度保守的基因，存在于节肢动物和哺乳动物等多种物种中。哺乳动物的SHH编码一种信号分子，在发育模式形成中起着核心作用，尤其是在神经系统和骨骼系统的发育中。在此，我们表明，相对于其他哺乳动物，SHH在灵长类动物中的分子进化明显加速。我们进一步表明，在灵长类动物中，这种加速在人类谱系中最为显著。最后，我们表明，人类谱系中的加速与适应性进化的特征相关联。特别是，人类谱系的特征是丝氨酸和苏氨酸的大量增加且在统计学上高度非随机，这些残基是翻译后修饰的潜在底物。这表明SHH在人类谱系中可能进化出了更复杂的翻译后调控。总的来说，这些发现表明SHH可能是灵长类或人类特异性神经和/或骨骼系统形态特征进化的潜在贡献者，并为进一步研究该关键发育基因的灵长类或人类特异性功能提供了动力。
