人類染色體組中，圍繞著遺傳基因,，存在著大量的“神秘”DNA,，其中大量被認為是“垃圾”，另有一些被稱為調(diào)控DNA（regulatory DNA）,，有助于基因的開啟或關(guān)閉,。美國科學家近日研究發(fā)現(xiàn)，這種調(diào)控DNA的量可能要比我們認識到的多得多,。相關(guān)論文12月10日在線發(fā)表于《基因組研究》（Genome Research）上,。
領(lǐng)導這一研究的是美國約翰·霍普金斯大學醫(yī)學院的Andrew McCallion。他的小組以與神經(jīng)發(fā)育有關(guān)的phox2b基因為研究對象,，運用新的實驗方法,，分析了大量的DNA片斷。結(jié)果發(fā)現(xiàn),，常規(guī)方法檢出的phox2b調(diào)控DNA量大約只是新方法的29%至61%,。
McCallion表示，此次研究支持了這樣一種觀點,，即許多調(diào)控蛋白的DNA序列并沒有被保留下來,。他同時希望新結(jié)果能說明類似的研究是有價值的。
而在接下來的研究中,，McCallion計劃分析其它神經(jīng)細胞的基因,。他說：“我認為我們剛剛開始認識到DNA調(diào)控片斷的重要性和豐富性，通過調(diào)節(jié)每個細胞內(nèi)基因的活性,，它們協(xié)助創(chuàng)造了人體內(nèi)豐富的細胞類型,。”（科學網(wǎng) 梅進/編譯）
原始出處:
Published online before print December 10, 2007
Genome Research, DOI: 10.1101/gr.6929408
Metrics of sequence constraint overlook regulatory sequences in an exhaustive analysis at phox2b
David M. McGaughey1, Ryan M. Vinton1, Jimmy Huynh1, Amr Al-Saif1, Michael A. Beer1,2, and Andrew S. McCallion1,3,4
1 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; 2 Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; 3 Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Despite its recognized utility, the extent to which evolutionary sequence conservation-based approaches may systematically overlook functional noncoding sequences remains unclear. We have tiled across sequence encompassing the zebrafish phox2b gene, ultimately evaluating 48 amplicons corresponding to all noncoding sequences therein for enhancer activity in zebrafish. Post hoc analyses of this interval utilizing five commonly used measures of evolutionary constraint (AVID, MLAGAN, SLAGAN, phastCons, WebMCS) demonstrate that each systematically overlooks regulatory sequences. These established algorithms detected only 29%–61% of our identified regulatory elements, consistent with the suggestion that many regulatory sequences may not be readily detected by metrics of sequence constraint. However, we were able to discriminate functional from nonfunctional sequences based upon GC composition and identified position weight matrices (PWM), demonstrating that, in at least one case, deleting sequences containing a subset of these PWMs from one identified regulatory element abrogated its regulatory function. Collectively, these data demonstrate that the noncoding functional component of vertebrate genomes may far exceed estimates predicated on evolutionary constraint.
