科研人員因還未了解人類(lèi)97%基因的功能,,只能將它們命名為“垃圾基因”。
最近,,本地科研團(tuán)體近發(fā)現(xiàn)這些“垃圾基因”可能是揭開(kāi)哺乳動(dòng)物進(jìn)化論之謎的核心線(xiàn)索,讓人們了解人類(lèi)與猩猩之間為什么產(chǎn)生差異,。但更有實(shí)際作用的是,,“垃圾基因”中可能有很多能控制癌癥和干細(xì)胞基因的DNA順序與蛋白質(zhì)組合。
新加坡基因組研究院(Genome Institute of Singapore)執(zhí)行署長(zhǎng)劉德斌教授說(shuō),,基因決定哺乳動(dòng)物的生存環(huán)境,,為了生存,哺乳動(dòng)物需要不斷進(jìn)化,,也就是在長(zhǎng)期繁殖時(shí)產(chǎn)生差異,,例如新一代比上一代更高大等,并衍生其他新種類(lèi),。當(dāng)突如其來(lái)的災(zāi)難,,例如旱災(zāi)或是彗星撞地球時(shí),一些哺乳動(dòng)物能憑特有的基因存活下來(lái),。但科研界對(duì)其進(jìn)化方式并不是十分了解,。
研究院高級(jí)組長(zhǎng)紀(jì)堯姆·布爾克(Guillaume Bourque)與組員,包括劉德斌等30人,,在最新一期的科學(xué)雜志《基因組研究》(Genome Research)發(fā)表了研究成果,。
報(bào)告主要說(shuō)明“垃圾基因”中有一些一直重復(fù)的脫氧核糖核酸(DNA)順序,,叫反轉(zhuǎn)錄轉(zhuǎn)座子(retrotransposon)。它們?cè)诿看芜M(jìn)化時(shí),,都在整個(gè)遺傳染色體中跳來(lái)跳去,,當(dāng)各種蛋白質(zhì)類(lèi)結(jié)構(gòu)的轉(zhuǎn)錄因子(transcription factor)把自己“捆綁”在這些重復(fù)的DNA順序時(shí),就能控制附近的基因,。
如果這些“捆綁”在一起的組合剛好能增強(qiáng)附近基因,,例如決定身高的基因,進(jìn)化出來(lái)的哺乳動(dòng)物就會(huì)更高,。而積少成多的種種變化,,例如眼睛顏色、智商,、聽(tīng)覺(jué)等,,就形成我們今天所見(jiàn)到的生物多樣化。
同樣的,,這些組合也能控制癌癥和干細(xì)胞基因,。劉德斌說(shuō),這次的報(bào)告說(shuō)明“垃圾基因”中可能有很多能控制癌癥和干細(xì)胞基因的DNA順序與蛋白質(zhì)組合,。
這次的研究把重點(diǎn)放在5個(gè)在癌癥和干細(xì)胞研究中相當(dāng)重要的轉(zhuǎn)錄因子身上,,它們有18%到33%的“捆綁”位置在“垃圾基因”里,而科研界已知的轉(zhuǎn)錄因子有2000多個(gè),,所以可以肯定這次的發(fā)現(xiàn)必定會(huì)為癌癥和干細(xì)胞研究造成重要影響,。
團(tuán)隊(duì)主要利用電腦科技分析DNA順序。劉德斌說(shuō),,與其他研究院比起來(lái),,新加坡基因組研究院的研究器材并不特別先進(jìn),團(tuán)隊(duì)是勝在知識(shí)智力方面,,他也用“比別人更聰明”來(lái)形容自己的隊(duì)伍,。
劉德斌也透露,團(tuán)隊(duì)下來(lái)將比較人類(lèi)與老鼠的轉(zhuǎn)錄因子,,因?yàn)榭蒲薪绯S美鲜笞鲈囼?yàn),,這種比較研究能為科研界提供更多信息。(生物谷Bioon.com)
生物谷推薦原始出處:
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.