生物谷报道:人类和黑猩猩的编码蛋白基因有99%是相同的,但二者的巨大差异是不言而喻的。这一现象的根源何在?美国科学家的一项最新研究表明,基因中的调控序列(Regulatory sequences)的变异速度远远超过编码蛋白基因,这在很大程度上决定着物种间的进化差异。相关论文发表在8月10日的《科学》杂志上。
传统观点认为,如果造成进化差异的不是基因的话,那一定就是调控基因表达的DNA片断。然而,要验证这一看法并不容易。即使在十分接近的物种之间,DNA调控区域或者启动子(promoter)的核苷酸序列也存在着巨大的差异性和可变性,而且要远远超过相应的编码蛋白基因间的差异。
领导最新研究的是美国耶鲁大学的分子和发育生物学家Michael Snyder。他的小组利用染色质免疫沉淀(chromatin immunoprecipitation)和微阵列分析(microarray analysis)技术,确定并且比较了3种十分接近的酵母菌的DNA调控差异。Snyder由此估计,基因调控元素的变异进化速度比普通基因序列高两个量级。
Snyder表示,“转录因子(transcription factors)会与基因调控序列的特殊位点绑定,从而控制编码蛋白基因的开与关。因此,通过分析转录因子特定的绑定位置,我们能够从功能上比较不同物种间特定基因调控类型的相似性和差异性。”
研究人员惊讶地发现,尽管这3种相近的酵母菌种类的基因序列差异很小,但它们之间的基因调控位点的差异却是广泛而巨大的。在3种酵母菌中,同一种转录因子绑定在相同位点的情况只占全部的20%左右。此外,在许多情况下,即使它们拥有相同的DNA绑定位点,仍会出现在一种酵母菌中能够与转录因子绑定,而在其他的酵母菌中则不能结合的情况。
Snyder表示,类似的研究将有望使人们弄清编码蛋白基因和基因调控之间的平衡,进而揭开人类和黑猩猩的差异之谜。(科学网 任霄鹏/编译)
原始出处:
Science 10 August 2007:
Vol. 317. no. 5839, pp. 815 - 819
DOI: 10.1126/science.1140748
Divergence of Transcription Factor Binding Sites Across Related Yeast Species
Anthony R. Borneman,1* Tara A. Gianoulis,2 Zhengdong D. Zhang,3 Haiyuan Yu,3 Joel Rozowsky,3 Michael R. Seringhaus,3 Lu Yong Wang,4 Mark Gerstein,2,3,5 Michael Snyder1,2,3
Characterization of interspecies differences in gene regulation is crucial for understanding the molecular basis of both phenotypic diversity and evolution. By means of chromatin immunoprecipitation and DNA microarray analysis, the divergence in the binding sites of the pseudohyphal regulators Ste12 and Tec1 was determined in the yeasts Saccharomyces cerevisiae, S. mikatae, and S. bayanus under pseudohyphal conditions. We have shown that most of these sites have diverged across these species, far exceeding the interspecies variation in orthologous genes. A group of Ste12 targets was shown to be bound only in S. mikatae and S. bayanus under pseudohyphal conditions. Many of these genes are targets of Ste12 during mating in S. cerevisiae, indicating that specialization between the two pathways has occurred in this species. Transcription factor binding sites have therefore diverged substantially faster than ortholog content. Thus, gene regulation resulting from transcription factor binding is likely to be a major cause of divergence between related species.
1 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
2 Program in Computational Biology, Yale University, New Haven, CT 06511, USA.
3 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
4 Integrated Data Systems Department, Siemens Corporate Research, Princeton, NJ 08540, USA.
5 Department of Computer Science, Yale University, New Haven, CT 06511, USA.
* Present address: Australian Wine Research Institute, Glen Osmond, Adelaide, SA 5064, Australia.
To whom correspondence should be addressed. E-mail: michael.snyder@yale.edu