Costas Javier, Casares Fernando, Vieira Jorge
Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Rua do Campo Alegre 823, 4150-180, Porto, Portugal.
Gene. 2003 May 22;310:215-20. doi: 10.1016/s0378-1119(03)00556-0.
Despite the importance of cis-regulatory regions in evolution, little is know about their evolutionary dynamics. In this report, we analyze the process of evolution of binding sites for transcription factors using as a model a well characterized system, the Drosophila early developmental enhancers. We compare the sequences of eight enhancer regions for early developmental genes between Drosophila melanogaster and other two species, Drosophila virilis and Drosophila pseudoobscura, searching for the presence/absence of 104 biochemically verified binding sites from D. melanogaster. We also modeled the binding specificity of each binding site by the use of well-defined positional weight matrices (PWMs). The comparisons showed that turnover of binding sites seems to fit a molecular clock, at an approximate rate of 0.94% of gain/loss of binding sites per million years. This intense turnover affects both high and low affinity binding sites at the same extent. Furthermore, the subset of overlapping binding sites is also subjected to this high turnover. Conserved binding sites seem to be constrained to maintain not only location but also the exact sequence at each particular position. Finally, we detected a significant decrease in mean PWM scores for the D. virilis binding sites in the case of Hunchback. Possible explanations for this fact are discussed.
尽管顺式调控区域在进化中很重要，但人们对其进化动态了解甚少。在本报告中，我们以一个特征明确的系统——果蝇早期发育增强子为模型，分析转录因子结合位点的进化过程。我们比较了黑腹果蝇与另外两个物种——粗壮果蝇和拟暗果蝇之间八个早期发育基因增强子区域的序列，寻找黑腹果蝇中104个经生化验证的结合位点的有无情况。我们还通过使用定义明确的位置权重矩阵（PWMs）对每个结合位点的结合特异性进行建模。比较结果表明，结合位点的更替似乎符合分子钟，更替速率约为每百万年结合位点增减0.94%。这种剧烈的更替对高亲和力和低亲和力结合位点的影响程度相同。此外，重叠结合位点的子集也经历了这种高更替率。保守的结合位点似乎不仅在位置上受到限制，而且在每个特定位置的精确序列也受到限制。最后，我们检测到在驼背蛋白的情况下，粗壮果蝇结合位点的平均PWM得分显著降低。我们讨论了这一事实的可能解释。
