科學(xué)家早已知道,，有些“垃圾”DNA（重復(fù)性DNA片段）能夠進(jìn)化成外顯子（exon）,，作為高等有機(jī)體內(nèi)編碼蛋白基因的構(gòu)成成分。美國(guó)科學(xué)家近日發(fā)現(xiàn)證據(jù)表明,，大量來自垃圾DNA的外顯子在基因調(diào)控中發(fā)揮著作用,。相關(guān)論文10月17日發(fā)表在《PloS遺傳學(xué)》（PLoS Genetics）上。
大約一半的人類DNA由重復(fù)性片段構(gòu)成,，其中包括轉(zhuǎn)座子（transposon）,，它能換位到基因組內(nèi)的不同位置。反轉(zhuǎn)錄轉(zhuǎn)座子（retrotransposon）可被轉(zhuǎn)錄入RNA,，之后被重整入基因組DNA,。人類基因組中最常見的反轉(zhuǎn)錄轉(zhuǎn)座子是Alu序列，它擁有超過100萬個(gè)拷貝,，占據(jù)了大約10%的人類基因組,。
論文高級(jí)作者、美國(guó)愛荷華大學(xué)醫(yī)學(xué)院的Yi Xing說：“Alu序列是新外顯子的主要來源,。Alu是靈長(zhǎng)類特異性的反轉(zhuǎn)錄轉(zhuǎn)座子,，從它制造外顯子可能有助于形成靈長(zhǎng)類的獨(dú)特特性，所以我們想要更好了解這一過程,。”
研究人員使用了高密度外顯子微矩陣技術(shù),，這一技術(shù)擁有將近6百萬個(gè)探針，用來監(jiān)測(cè)人類所有外顯子的表達(dá)模式,。研究人員利用所得數(shù)據(jù),，分析了11個(gè)人類組織中330個(gè)來源于Alu的外顯子，鑒別出許多具有令人感興趣的表達(dá)和功能特性的外顯子,。
論文第一作者、愛荷華大學(xué)內(nèi)科醫(yī)學(xué)系的Lan Lin說：“人類基因組中的數(shù)百個(gè)外顯子都是來自于Alu序列,，全基因組外顯子微矩陣技術(shù)使我們能夠快速鑒別出最可能有助于調(diào)控基因表達(dá)和功能的外顯子,。”
對(duì)人類的一個(gè)基因SEPN1（與肌肉營(yíng)養(yǎng)失調(diào)有關(guān)）的分析，對(duì)照來自黑猩猩和短尾猿組織的數(shù)據(jù),，表明,，一個(gè)來源于Alu的肌肉特異性外顯子是來源于人類和黑猩猩進(jìn)化分歧后發(fā)生的人類特異性改變。
Xing表示：“這樣來看，這個(gè)外顯子僅僅在人類肌肉中高水平表達(dá),，而在任何其它人類組織或非人類靈長(zhǎng)類組織中均不是這樣,。這意味著這個(gè)外顯子在肌肉中扮演了功能性角色，而這一作用是人類特異性的,。”（生物谷Bioon.com）
生物谷推薦原始出處：
PLoS Genetics,，doi:10.1371/journal.pgen.1000225，Lan Lin,，Yi Xing
Diverse Splicing Patterns of Exonized Alu Elements in Human Tissues
Lan Lin1, Shihao Shen2, Anne Tye1, James J. Cai3, Peng Jiang1, Beverly L. Davidson1,4,5, Yi Xing1,6*
1 Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America, 2 Department of Biostatistics, University of Iowa, Iowa City, Iowa, United States of America, 3 Department of Biology, Stanford University, Stanford, California, United States of America, 4 Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, United States of America, 5 Department of Neurology, University of Iowa, Iowa City, Iowa, United States of America, 6 Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States of America
Abstract
Exonization of Alu elements is a major mechanism for birth of new exons in primate genomes. Prior analyses of expressed sequence tags show that almost all Alu-derived exons are alternatively spliced, and the vast majority of these exons have low transcript inclusion levels. In this work, we provide genomic and experimental evidence for diverse splicing patterns of exonized Alu elements in human tissues. Using Exon array data of 330 Alu-derived exons in 11 human tissues and detailed RT-PCR analyses of 38 exons, we show that some Alu-derived exons are constitutively spliced in a broad range of human tissues, and some display strong tissue-specific switch in their transcript inclusion levels. Most of such exons are derived from ancient Alu elements in the genome. In SEPN1, mutations of which are linked to a form of congenital muscular dystrophy, the muscle-specific inclusion of an Alu-derived exon may be important for regulating SEPN1 activity in muscle. Realtime qPCR analysis of this SEPN1 exon in macaque and chimpanzee tissues indicates human-specific increase in its transcript inclusion level and muscle specificity after the divergence of humans and chimpanzees. Our results imply that some Alu exonization events may have acquired adaptive benefits during the evolution of primate transcriptomes.
