科学家早已知道，有些“垃圾”DNA（重复性DNA片段）能够进化成外显子（exon），作为高等有机体内编码蛋白基因的构成成分。美国科学家近日发现证据表明，大量来自垃圾DNA的外显子在基因调控中发挥着作用。相关论文10月17日发表在《PloS遗传学》（PLoS Genetics）上。
大约一半的人类DNA由重复性片段构成，其中包括转座子（transposon），它能换位到基因组内的不同位置。反转录转座子（retrotransposon）可被转录入RNA，之后被重整入基因组DNA。人类基因组中最常见的反转录转座子是Alu序列，它拥有超过100万个拷贝，占据了大约10%的人类基因组。
论文高级作者、美国爱荷华大学医学院的Yi Xing说：“Alu序列是新外显子的主要来源。Alu是灵长类特异性的反转录转座子，从它制造外显子可能有助于形成灵长类的独特特性，所以我们想要更好了解这一过程。”
研究人员使用了高密度外显子微矩阵技术，这一技术拥有将近6百万个探针，用来监测人类所有外显子的表达模式。研究人员利用所得数据，分析了11个人类组织中330个来源于Alu的外显子，鉴别出许多具有令人感兴趣的表达和功能特性的外显子。
论文第一作者、爱荷华大学内科医学系的Lan Lin说：“人类基因组中的数百个外显子都是来自于Alu序列，全基因组外显子微矩阵技术使我们能够快速鉴别出最可能有助于调控基因表达和功能的外显子。”
对人类的一个基因SEPN1（与肌肉营养失调有关）的分析，对照来自黑猩猩和短尾猿组织的数据，表明，一个来源于Alu的肌肉特异性外显子是来源于人类和黑猩猩进化分歧后发生的人类特异性改变。
Xing表示：“这样来看，这个外显子仅仅在人类肌肉中高水平表达，而在任何其它人类组织或非人类灵长类组织中均不是这样。这意味着这个外显子在肌肉中扮演了功能性角色，而这一作用是人类特异性的。”（生物谷Bioon.com）
生物谷推荐原始出处：
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.
