人類基因組有大量的DNA被視為基因組垃圾,，最近斯坦福大學(xué)醫(yī)學(xué)院和圣塔克魯茲-加州大學(xué)（University of California - Santa Cruz）的研究人員發(fā)現(xiàn)，這些垃圾DNA也攜帶重要信息,，控制基因的開/關(guān)時間,。具體研究內(nèi)容刊登于4月23日《PNAS》。
斯坦福大學(xué)發(fā)育生物學(xué)和計算機科學(xué)副教授Gill Bejerano發(fā)現(xiàn)人類染色體上點綴著1萬多個近似的片段,，這些片段大部分位于被稱為“基因沙漠”的無基因染色體區(qū),。實際上，這些片段攜帶許多有用的DNA小塊,，其中就包括被Bejerano等命名為“regulatory jungles”的DNA塊,。
Bejerano等發(fā)現(xiàn)，大多數(shù)鄰近基因的DNA片段在胚胎發(fā)育頭幾周發(fā)揮調(diào)節(jié)作用,，調(diào)節(jié)基因作用的時間和地點,，并且在細胞粘附相關(guān)基因的周圍含量豐富，幫助細胞遷移到正確位點,，正確排列為組織和器官,。
Bejerano等研究的10402個片段是轉(zhuǎn)座子的殘體。如果一個轉(zhuǎn)座子插入到一個不必要的地方,，會慢慢地累積突變直到與原始序列無相似之處,，基因組充滿了這些“衰敗”的轉(zhuǎn)位子。如果一個轉(zhuǎn)座子插入一個需要它的地方,，會保持原始序列,，為其篩選提供了可能。Bejerano等曾經(jīng)鑒別出許多似乎對鄰近基因有調(diào)節(jié)作用的轉(zhuǎn)座子,，但不知道這種現(xiàn)象發(fā)生的頻率,。Bejerano說轉(zhuǎn)座子也許是推動進化的主動力。
Bejerano的成功受益于兩大成果：多個脊椎動物的全基因組測序結(jié)果公布和遺傳分析軟件的技術(shù)進步,。實際上,，Bejerano并不是第一個提出轉(zhuǎn)座子有調(diào)節(jié)鄰近基因作用的人，諾貝爾獎獲得者Barbara McClintock博士（轉(zhuǎn)位子的發(fā)現(xiàn)者）早在1956年便提出轉(zhuǎn)座子能夠幫助鄰近基因確定開關(guān)時間,。
英文原文：
'Junk' DNA Now Looks Like Powerful Regulator, Scientists Find
Science Daily—Large swaths of garbled human DNA once dismissed as junk appear to contain some valuable sections, according to a new study by researchers at the Stanford University School of Medicine and the University of California-Santa Cruz. The scientists propose that this redeemed DNA plays a role in controlling when genes turn on and off.
Gill Bejerano, PhD, assistant professor of developmental biology and of computer science at Stanford, found more than 10,000 nearly identical genetic snippets dotting the human chromosomes. Many of those snippets were located in gene-free chromosomal expanses once described by geneticists as "gene deserts." These sections are, in fact, so clogged with useful DNA bits - including the ones Bejerano and his colleagues describe - that they've been renamed "regulatory jungles."
"It's funny how quickly the field is now evolving," Bejerano said. His work picking out these snippets and describing why they might exist will be published in the April 23 advance online issue of the Proceedings of the National Academy of Sciences.
It turns out that most of the segments described in the research paper cluster near genes that play a carefully orchestrated role during an animal's first few weeks after conception. Bejerano and his colleagues think that these sequences help in the intricate choreography of when and where those genes flip on as the animal lays out its body plan. In particular, the group found the sequences to be especially abundant near genes that help cells stick together. These genes play a crucial role early in an animal's life, helping cells migrate to the correct location or form. into organs and tissues of the correct shape.
The 10,402 sequences studied by Bejerano, along with David Haussler, PhD, professor of biomolecular engineering at UC-Santa Cruz, are remnants of unusual DNA pieces called transposons that duplicate themselves and hop around the genome. "We used to think they were mostly messing things up. Here is a case where they are actually useful," Bejerano said.
He suspects that when a transposon is plopped down in a region where it wasn't needed, it slowly accumulated mutations until it no longer resembled its original sequence. The genome is littered with these decaying transposons. When a transposon dropped into a location where it was useful, however, it held on to much of the original sequence, making it possible for Bejerano to pick out.
In past work, Bejerano and his co-workers had identified a handful of transposons that seemed to regulate nearby genes. However, it wasn't clear how common the phenomenon might be. "Now we've shown that transposons may be a major vehicle for evolutionary novelty," he said.
The paper's first author, Craig Lowe, a graduate student in Haussler's lab at UC-Santa Cruz, said finding the transposons was just the first step. "Now we are trying to nail down exactly what the elements are doing," he said.
Bejerano's work wouldn't have been possible without two things that became available over the past few years: the complete gene sequence of many vertebrate species, and fast computers running sophisticated new genetic analysis software. "Right now it's like being a kid in a candy warehouse," Bejerano said. Computer-savvy biologists have the tools to ask questions about how genes and chromosomes evolve and change, questions that just a few years ago were unanswerable.
Bejerano and his colleagues aren't the first to suggest that transposons play a role in regulating nearby genes. In fact, Nobel laureate Barbara McClintock, PhD, who first discovered transposons, proposed in 1956 that they could help determine the timing for when nearby genes turn on and off.
Funding for the study came through Haussler, who is a Howard Hughes Medical Institute investigator.
Note: This story has been adapted from a news release issued by Stanford University Medical Center.
