生物谷報道：人類和黑猩猩的編碼蛋白基因有99%是相同的，但二者的巨大差異是不言而喻的,。這一現(xiàn)象的根源何在,？美國科學家的一項最新研究表明，基因中的調(diào)控序列（Regulatory sequences）的變異速度遠遠超過編碼蛋白基因,，這在很大程度上決定著物種間的進化差異,。相關(guān)論文發(fā)表在8月10日的《科學》雜志上。
傳統(tǒng)觀點認為,，如果造成進化差異的不是基因的話,，那一定就是調(diào)控基因表達的DNA片斷。然而,，要驗證這一看法并不容易,。即使在十分接近的物種之間，DNA調(diào)控區(qū)域或者啟動子（promoter）的核苷酸序列也存在著巨大的差異性和可變性，而且要遠遠超過相應的編碼蛋白基因間的差異,。
領(lǐng)導最新研究的是美國耶魯大學的分子和發(fā)育生物學家Michael Snyder,。他的小組利用染色質(zhì)免疫沉淀（chromatin immunoprecipitation）和微陣列分析（microarray analysis）技術(shù)，確定并且比較了3種十分接近的酵母菌的DNA調(diào)控差異,。Snyder由此估計,，基因調(diào)控元素的變異進化速度比普通基因序列高兩個量級。
Snyder表示,，“轉(zhuǎn)錄因子（transcription factors）會與基因調(diào)控序列的特殊位點綁定,，從而控制編碼蛋白基因的開與關(guān),。因此,，通過分析轉(zhuǎn)錄因子特定的綁定位置，我們能夠從功能上比較不同物種間特定基因調(diào)控類型的相似性和差異性,。”
研究人員驚訝地發(fā)現(xiàn),，盡管這3種相近的酵母菌種類的基因序列差異很小，但它們之間的基因調(diào)控位點的差異卻是廣泛而巨大的,。在3種酵母菌中,，同一種轉(zhuǎn)錄因子綁定在相同位點的情況只占全部的20%左右。此外,，在許多情況下,，即使它們擁有相同的DNA綁定位點，仍會出現(xiàn)在一種酵母菌中能夠與轉(zhuǎn)錄因子綁定,，而在其他的酵母菌中則不能結(jié)合的情況,。
Snyder表示，類似的研究將有望使人們弄清編碼蛋白基因和基因調(diào)控之間的平衡,，進而揭開人類和黑猩猩的差異之謎,。（科學網(wǎng) 任霄鵬/編譯）
原始出處:
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: [email protected]
