Centro Andaluz de Biología del Desarrollo (CABD), CSIC-Universidad Pablo de Olavide-Junta de Andalucía, Ctra. Utrera Km 1, Seville 41013, Spain.
BMC Genomics. 2012 Dec 19;13:713. doi: 10.1186/1471-2164-13-713.
Phenotypic evolution in animals is thought to be driven in large part by differences in gene expression patterns, which can result from sequence changes in cis-regulatory elements (cis-changes) or from changes in the expression pattern or function of transcription factors (trans-changes). While isolated examples of trans-changes have been identified, the scale of their overall contribution to regulatory and phenotypic evolution remains unclear.
Here, we attempt to examine the prevalence of trans-effects and their potential impact on gene expression patterns in vertebrate evolution by comparing the function of identical human tissue-specific enhancer sequences in two highly divergent vertebrate model systems, mouse and zebrafish. Among 47 human conserved non-coding elements (CNEs) tested in transgenic mouse embryos and in stable zebrafish lines, at least one species-specific expression domain was observed in the majority (83%) of cases, and 36% presented dramatically different expression patterns between the two species. Although some of these discrepancies may be due to the use of different transgenesis systems in mouse and zebrafish, in some instances we found an association between differences in enhancer activity and changes in the endogenous gene expression patterns between mouse and zebrafish, suggesting a potential role for trans-changes in the evolution of gene expression.
In total, our results: (i) serve as a cautionary tale for studies investigating the role of human enhancers in different model organisms, and (ii) suggest that changes in the trans environment may play a significant role in the evolution of gene expression in vertebrates.
人们认为动物的表型进化在很大程度上是由基因表达模式的差异驱动的，这些差异可能是由于顺式调控元件（顺式变化）中的序列变化，或者转录因子的表达模式或功能变化（反式变化）。虽然已经发现了孤立的反式变化的例子，但它们对调控和表型进化的总体贡献的规模仍不清楚。
在这里，我们试图通过比较两个高度分化的脊椎动物模型系统，即小鼠和斑马鱼中相同的人类组织特异性增强子序列的功能，来研究反式效应的普遍性及其对脊椎动物进化中基因表达模式的潜在影响。在 47 个经过测试的人类保守非编码元件（CNEs）中，在转基因小鼠胚胎和稳定的斑马鱼系中，至少在大多数（83%）情况下观察到一个物种特异性的表达域，而 36%的情况下在这两个物种之间呈现出截然不同的表达模式。尽管这些差异中的一些可能是由于在小鼠和斑马鱼中使用了不同的转基因系统，但在某些情况下，我们发现增强子活性的差异与小鼠和斑马鱼之间内源性基因表达模式的差异之间存在关联，这表明反式变化在基因表达的进化中可能起作用。
总的来说，我们的结果：（i）对研究人类增强子在不同模式生物中的作用的研究是一个警示；（ii）表明反式环境的变化可能在脊椎动物基因表达的进化中起重要作用。
