据9月4日的《科学》杂志报道说，研究人员已经在人类的基因组中发现了一段非编码序列，该序列可以增进发育中的手和前肢的基因表达，特别是在手腕和拇指连接的地方。根据ShyamPrabhakar 及其同僚披露，与黑猩猩和恒河猴相比，这一被称作HACNS1 的序列在人类中发生了迅速的演化，它可能对我们的手和脚的“人类化”扮演了某种角色。通过创制具有HACNS1 序列的小鼠胚胎，研究人员能够观察到它在前肢和后肢的发育中对基因表达的影响，但人们仍然不清楚的是哪一个基因或哪些基因是该序列的标靶。但是，HACNS1 的“增强子”功能好像确实是人类所独有的。
某些基因受到多种增强子序列的作用，其中包括某些与主要的增强子具有同样职责但却被发现距离标靶基因很远的增强子。Joung-Woo Hong 及其同僚的果蝇研究表明，这些“影子增强子”比它们的相关主要增强子要进化得更快，从而开启了人们通往调节某一特定基因而又不破坏其核心功能的新的方法之门。在一则相关的Perspective 中，Gregory Wray 和 Courtney Babbitt 讨论了Prabhakar, Hong 及其同僚是如何应对搜寻基因组中的具有深远调节影响的非编码区域的挑战的。（生物谷Bioon.com）
生物谷推荐原始出处：
Science 5 September 2008: Vol. 321. no. 5894, pp. 1346 - 1350 DOI: 10.1126/science.1159974
Human-Specific Gain of Function in a Developmental Enhancer
Shyam Prabhakar,1* Axel Visel,1 Jennifer A. Akiyama,1 Malak Shoukry,1 Keith D. Lewis,1Amy Holt,1Ingrid Plajzer-Frick,1 Harris Morrison,2 David R. FitzPatrick,2 Veena Afzal,1 Len A. Pennacchio,1,3Edward M. Rubin,1,3James P. Noonan1
Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81–base pair module otherwise highly constrainedamong terrestrial vertebrates were sufficient to confer the human-specific limb expression domain.
1 Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
2 MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
3 United States Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.
