Science Focus (issue 022)

which are proteins that bind to specific regions of DNA to regulate the transcription of the gene nearby (footnote 2). A study on human and mouse cell lines revealed that, for the 26 TFs examined, around 20% of transcription factor binding sites are embedded in TEs [5]. The insertion of TEs into the genome may have provided a novel way for the cell to exert a finer control on gene expression. From an unaccepted discovery to one of the most impor tant concepts in modern genet ics, transposable elements have revolutionized our understanding on genomes and evolution. We often see novel observable traits appear as the results of evolution as species adapting to the external environment, but transposable elements taught us that the evolution of genomes is also in action deep inside the cell. 1 Editor’s remark: Let us go beyond the curriculum for a while – phenotype is not only determined by genetic sequence or allele. This is a field in biology called “epigenetics”, which is defined as the study of phenotypical changes without alternations in the DNA sequence. 2 Transcription factor: DNA-binding proteins, which bind to specific DNA sequences to either facilitate or repress transcription. For example, you will learn in undergraduate courses that, in eukaryotes, a class of TFs called general transcription factors (GTFs) is required to initiate transcription by helping RNA polymerases locate the start site. It sits on the DNA before RNA polymerase comes. TFs can also control where and when a gene is turned on. 在第十八期,我們向大家介紹過轉位子(transposable elements)的概念及其發現者 Barbara McClintock。也許 你會認為 DNA 能在基因組內跳來跳去,並插入其他位置是 一件很瘋狂的事。然而,轉位子還有更多奇特的地方。本文 將告訴你一些有關轉位子最有趣的事情,以及它們除了跳躍 外的實質功用。 分類及起源 轉位子可根據其插入機制分為兩種類型。I 型轉位子又 名反轉錄轉位子(retrotransposons),它們通過「複製 後貼上(copy-and-paste)」的機制在基因組內跳來跳 去。這些反轉錄轉位子首先會被轉錄成 RNA,然後反轉錄 成 DNA。過程中複製出一段與原來反轉錄轉位子相同的 DNA,新合成的 DNA 複本會插入基因組中。II 型轉位子則 通過「剪下後貼上(cut-and-paste)」的機制把自己重新 插入至基因組。II 型轉位子會從原來位置被切出,在轉位酶 (transposase)協助下重新插入基因組另一個位置。所有 轉位子加起來佔人類基因組約 50% [1],儘管在演化過程中 大多數轉位子都已經失去跳躍能力。 如果你熟悉病毒感染的機制,你可能會發現它們頗為 相似。的確,反轉錄轉位子和反轉錄病毒有著許多相似之 處,例如它們能將由反轉錄合成而來的 DNA 插入宿主基因 組。事實上,內源性反轉錄病毒(endogenous retrovirus (ERV);它不是一種反轉錄病毒,而是我們基因組中的病毒 DNA)是其中一種反轉錄轉位子,它是數百萬年前病毒多次 感染生殖細胞後遺留下來的 DNA。病毒基因組就此進入了 我們祖先的基因組內,並遺傳至後世。內源性反轉錄病毒約 佔人類基因組的 7-8% [2]。總而言之,人類的基因組中充斥 著病毒的 DNA。(但請注意,並不是所有反轉錄轉位子都證 實來自病毒。) 調控及適應 人類基因組中存在病毒基因和DNA 能跳來跳去這兩個 事實大概會使不少人感到震驚,而這樣也可能會為我們帶來 危險。如果宿主沒有發展出抑制病毒 DNA 轉位和轉錄的 機制,宿主就有發生基因突變和再次感染的風險。轉位子貿 然插入基因組內已知有用的序列,或病毒蛋白得以表達都可 能對宿主有害。可幸的是,我們身體有多種抑制轉位子的機 制,以確保我們的安全。基因表達很大程度上取決於 DNA 的開放程度(accessibility),如果一段 DNA 的是開放的,

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