Science Focus (issue 022)

17 融為一體的不速之客 轉位子與基因組演化 I nvade and Adapt Genome Evolut i on via Transposable Elements By Kit Kan 簡迎曦 In Issue 018, we introduced you to the concept of transposable elements and its discoverer, Barbara McClintock. Maybe you find it crazy that our DNA can jump around the genome, creat ing new insertions. Sti l l, there are many more fascinating things about these elements. This article will take you through some of the most intriguing things about transposable elements and what they do other than jumping around. Classification and Origin Transposable elements (TEs) can be classified into two types based on their mechanism of insertion. Class 1 TEs are cal led ret rotransposons. These elements jump around the genome by a copy-andpaste mechanism. The retrotransposons are fi rst transcribed into an RNA intermediate, then reverse transcribed into DNA. This process creates a DNA segment identical to the original retrotransposon. The DNA copy is then integrated into the genome to create a new inser tion. Class 2 TEs are DNA transposons that can be cut and pasted without amplification. A DNA transposon is excised from the original position and re-integrated into another part of the genome with the help of an enzyme called transposase. All TEs together make up around 50% of the human genome [1], although, throughout evolutionary, most have lost their abi l ity to jump around. If you are familiar with the mechanism of viral infection, you may see some resemblance between these mechani sms . Indeed, ret rot ransposons and a par ticular type of vi rus, retrovi rus, share many similarities, such as the ability to insert their DNA, synthesized from reverse transcription, into the host genome. In fact, endogenous retrovirus (ERV; not retrovirus but viral DNA in our genome) are a type of ret rot ransposon, which are the remnants of vi ral germ- l ine infections mi l l ions of years ago. The viral genome was integrated into our ancestors’ genome and passed on to future generations. ERVs make up around 7-8% of the human genome [2]. In short, we are part human and part virus. (Note that not all retrotransposons can be d i r ec t l y t raced to a v i ra l o r i g i n . ) Regulation and Adaptation While having viral DNA in our genome and DNA jumping around surely stun most people, these features could also be dangerous. If the host does not develop a mechanism to suppress transposition and transcription of viral DNA, it risks mutation and reinfection. Insertion of TEs into functional sequences in the genome or expression of viral proteins may cause harmful effects to the host. Luckily, our body has multiple repression mechanisms against TEs to keep us safe. The expression of genes depends greatly on the accessibility of the DNA. If a segment of DNA is open, machineries required for transcription, such as RNA polymerase, can bind to that segment and activate transcription to express the gene. However, when the DNA is condensed, those machineries cannot bind and that region of DNA is repressed (footnote 1). Epigenetic modifications are some of the ways in which TEs are repressed through altering DNA accessibility [1]. When these mechanisms are faulty, diseases may arise. Dysregulated TEs has been shown to cause neuronal death [3], hemophilia [4] and cancer. Since most TEs are repressed and thought to be harmful to the host, for a very long time, they were called “junk DNA”, as they appear to be nonfunctional and solely parasitic. However, in recent years, some TEs are found to be adapted into the host genome to perform certain functions. Some TEs serve as binding sites for transcription factors (TFs),