科研人员因还未了解人类97%基因的功能,只能将它们命名为“垃圾基因”。
最近,本地科研团体近发现这些“垃圾基因”可能是揭开哺乳动物进化论之谜的核心线索,让人们了解人类与猩猩之间为什么产生差异。但更有实际作用的是,“垃圾基因”中可能有很多能控制癌症和干细胞基因的DNA顺序与蛋白质组合。
新加坡基因组研究院(Genome Institute of Singapore)执行署长刘德斌教授说,基因决定哺乳动物的生存环境,为了生存,哺乳动物需要不断进化,也就是在长期繁殖时产生差异,例如新一代比上一代更高大等,并衍生其他新种类。当突如其来的灾难,例如旱灾或是彗星撞地球时,一些哺乳动物能凭特有的基因存活下来。但科研界对其进化方式并不是十分了解。
研究院高级组长纪尧姆·布尔克(Guillaume Bourque)与组员,包括刘德斌等30人,在最新一期的科学杂志《基因组研究》(Genome Research)发表了研究成果。
报告主要说明“垃圾基因”中有一些一直重复的脱氧核糖核酸(DNA)顺序,叫反转录转座子(retrotransposon)。它们在每次进化时,都在整个遗传染色体中跳来跳去,当各种蛋白质类结构的转录因子(transcription factor)把自己“捆绑”在这些重复的DNA顺序时,就能控制附近的基因。
如果这些“捆绑”在一起的组合刚好能增强附近基因,例如决定身高的基因,进化出来的哺乳动物就会更高。而积少成多的种种变化,例如眼睛颜色、智商、听觉等,就形成我们今天所见到的生物多样化。
同样的,这些组合也能控制癌症和干细胞基因。刘德斌说,这次的报告说明“垃圾基因”中可能有很多能控制癌症和干细胞基因的DNA顺序与蛋白质组合。
这次的研究把重点放在5个在癌症和干细胞研究中相当重要的转录因子身上,它们有18%到33%的“捆绑”位置在“垃圾基因”里,而科研界已知的转录因子有2000多个,所以可以肯定这次的发现必定会为癌症和干细胞研究造成重要影响。
团队主要利用电脑科技分析DNA顺序。刘德斌说,与其他研究院比起来,新加坡基因组研究院的研究器材并不特别先进,团队是胜在知识智力方面,他也用“比别人更聪明”来形容自己的队伍。
刘德斌也透露,团队下来将比较人类与老鼠的转录因子,因为科研界常用老鼠做试验,这种比较研究能为科研界提供更多信息。(生物谷Bioon.com)
生物谷推荐原始出处:
Genome Res. 2008. 18: 1752-1762 doi:10.1101/gr.080663.108
Evolution of the mammalian transcription factor binding repertoire via transposable elements
Guillaume Bourque1,5, Bernard Leong1, Vinsensius B. Vega1, Xi Chen2, Yen Ling Lee3, Kandhadayar G. Srinivasan3, Joon-Lin Chew2, Yijun Ruan3, Chia-Lin Wei3, Huck Hui Ng2, and Edison T. Liu4
1 Computational and Mathematical Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
2 Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
3 Genome Technology and Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
4 Cancer Biology and Pharmacology, Genome Institute of Singapore, Singapore 138672, Singapore
Identification of lineage-specific innovations in genomic control elements is critical for understanding transcriptional regulatory networks and phenotypic heterogeneity. We analyzed, from an evolutionary perspective, the binding regions of seven mammalian transcription factors (ESR1, TP53, MYC, RELA, POU5F1, SOX2, and CTCF) identified on a genome-wide scale by different chromatin immunoprecipitation approaches and found that only a minority of sites appear to be conserved at the sequence level. Instead, we uncovered a pervasive association with genomic repeats by showing that a large fraction of the bona fide binding sites for five of the seven transcription factors (ESR1, TP53, POU5F1, SOX2, and CTCF) are embedded in distinctive families of transposable elements. Using the age of the repeats, we established that these repeat-associated binding sites (RABS) have been associated with significant regulatory expansions throughout the mammalian phylogeny. We validated the functional significance of these RABS by showing that they are over-represented in proximity of regulated genes and that the binding motifs within these repeats have undergone evolutionary selection. Our results demonstrate that transcriptional regulatory networks are highly dynamic in eukaryotic genomes and that transposable elements play an important role in expanding the repertoire of binding sites.