Wray Gregory A, Hahn Matthew W, Abouheif Ehab, Balhoff James P, Pizer Margaret, Rockman Matthew V, Romano Laura A
Department of Biology, Duke University, USA.
Mol Biol Evol. 2003 Sep;20(9):1377-419. doi: 10.1093/molbev/msg140. Epub 2003 May 30.
Gene expression is central to the genotype-phenotype relationship in all organisms, and it is an important component of the genetic basis for evolutionary change in diverse aspects of phenotype. However, the evolution of transcriptional regulation remains understudied and poorly understood. Here we review the evolutionary dynamics of promoter, or cis-regulatory, sequences and the evolutionary mechanisms that shape them. Existing evidence indicates that populations harbor extensive genetic variation in promoter sequences, that a substantial fraction of this variation has consequences for both biochemical and organismal phenotype, and that some of this functional variation is sorted by selection. As with protein-coding sequences, rates and patterns of promoter sequence evolution differ considerably among loci and among clades for reasons that are not well understood. Studying the evolution of transcriptional regulation poses empirical and conceptual challenges beyond those typically encountered in analyses of coding sequence evolution: promoter organization is much less regular than that of coding sequences, and sequences required for the transcription of each locus reside at multiple other loci in the genome. Because of the strong context-dependence of transcriptional regulation, sequence inspection alone provides limited information about promoter function. Understanding the functional consequences of sequence differences among promoters generally requires biochemical and in vivo functional assays. Despite these challenges, important insights have already been gained into the evolution of transcriptional regulation, and the pace of discovery is accelerating.
基因表达是所有生物体中基因型与表型关系的核心，并且它是表型各个方面进化变化的遗传基础的重要组成部分。然而，转录调控的进化仍未得到充分研究且了解甚少。在此，我们综述启动子序列（即顺式调控序列）的进化动态以及塑造它们的进化机制。现有证据表明，群体在启动子序列中蕴藏着广泛的遗传变异，其中相当一部分变异对生化和生物体表型都有影响，并且部分这种功能性变异会通过选择进行筛选。与蛋白质编码序列一样，启动子序列进化的速率和模式在不同基因座和不同进化枝之间存在很大差异，原因尚不清楚。研究转录调控的进化带来了一些经验性和概念性挑战，这些挑战超出了编码序列进化分析中通常遇到的挑战：启动子组织远不如编码序列规则，并且每个基因座转录所需的序列位于基因组中的多个其他基因座上。由于转录调控具有强烈的上下文依赖性，仅通过序列检查提供的启动子功能信息有限。了解启动子之间序列差异的功能后果通常需要生化和体内功能测定。尽管存在这些挑战，但我们已经在转录调控的进化方面获得了重要见解，并且发现的速度正在加快。
