Franchini Lucia F, de Souza Flavio S J, Low Malcolm J, Rubinstein Marcelo
Mob Genet Elements. 2012 Mar 1;2(2):106-109. doi: 10.4161/mge.20267.
The proopiomelanocortin (Pomc) gene encodes a prepropeptide with essential functions in the response to stress and energy balance, which is expressed in the pituitary and hypothalamus of vertebrate animals. Neuronal expression of Pomc is controlled by two distal enhancers named nPE1 and nPE2. Using transgenic mice, we observed that both enhancers drive identical expression patterns in the mammalian hypothalamus, starting at embryonic day 10.5, when endogenous Pomc expression commences. This overlapping enhancer activity is maintained throughout hypothalamic development and into adulthood. We also found that nPE1 and nPE2 were exapted as neuronal enhancers into the POMC locus after the sequential insertion of two unrelated retroposons. Thus, nPE1 and nPE2 are functional analogs and represent an authentic first example of convergent molecular evolution of cell-specific transcriptional enhancers. In this Commentary we discuss the following questions that remain unanswered: (1) how does transcriptional control of POMC operate in hypothalamic neurons of non-mammalian vertebrates? (2) What evolutionary forces are maintaining two discrete neuronal POMC enhancers under purifying selection for the last ~100 million years in all placental mammals? (3) What is the contribution of MaLRs to genome evolution?
阿黑皮素原（Pomc）基因编码一种前体肽，在应激反应和能量平衡中具有重要功能，在脊椎动物的垂体和下丘脑中表达。Pomc的神经元表达受两个远端增强子nPE1和nPE2控制。利用转基因小鼠，我们观察到这两个增强子在哺乳动物下丘脑中驱动相同的表达模式，从胚胎第10.5天开始，此时内源性Pomc表达开始。这种重叠的增强子活性在整个下丘脑发育过程中一直保持到成年。我们还发现，在两个不相关的反转录转座子相继插入后，nPE1和nPE2作为神经元增强子被纳入POMC基因座。因此，nPE1和nPE2是功能类似物，代表了细胞特异性转录增强子趋同分子进化的一个真实首例。在这篇评论中，我们讨论以下尚未得到解答的问题：（1）在非哺乳动物脊椎动物的下丘脑神经元中，POMC的转录控制是如何运作的？（2）在过去约1亿年里，在所有胎盘哺乳动物的纯化选择下，维持两个离散的神经元POMC增强子的进化力量是什么？（3）MaLRs对基因组进化有什么贡献？
