轉位因子(跳躍基因)在靈長類基因體的演化分析研究

Abstract

在多年來的研究中我們已經知道，人類的基因體有一半以上都是由重複片段序列所組成。這些重複片段中絕大多數都是轉位因子(跳躍基因)，包括轉位子(transposon)與反轉錄轉位子(retrotransposon)。其中Alu(一種靈長類特有的反轉錄轉位子)與LINE 1(另一種反轉錄轉位子)合計佔了人類基因體的27%。過去這些轉位因子常被認為是沒有用的垃圾DNA或是自私的DNA。然而，在最近的一篇報導中顯示，在人類的第19條染色體上有一個聚集了許多Alu單元以及許多靈長類特有的微小核醣核酸(microRNA)的叢集片段，此片段被命名為C19MC。我們提出一個假設，這個叢集的起源可能是來自一連串的序列複製事件造成。雖然這些微小核醣核酸的功能未知，但是靈長類的起源很可能和C19MC的形成有很大的關係。而C19MC很可能是透過Alu媒介的一連串複製機制所形成。因此我們很有興趣想要了解C19MC的演化歷史。透過分析每一個歷史事件，我們就有機會提出一個可能的模型來解釋C19MC形成的機制。這個研究也許可以幫助了解轉位因子與微小核醣核酸交互作用的關係。進一步地，我們也想研究在其它模式物種中是否也有類似的現象與機制。 本計畫另一個主題是研究鑲嵌在靈長類LINE 1中的簡單重覆序列(微衛星)的演化機制。由於微衛星的演化速率很快，辨識分化距離較遠的物種間的同源微衛星並不容易。也因此通常不容易得到足夠量的同源微衛星資料以建立可靠的微衛星演化模型。還好我們在之前的研究發現在LINE 1的某個特定的位置經常鑲嵌了一段簡單重覆序列，這些簡單重覆序列的長度和組成在LINE 1之間可以有很大的變異。由於所有的LINE 1都可以正確的排序(align)並依此建立可靠的演化樹，我們可以因此知道這些嵌在LINE 1中的大量簡單重覆序列(微衛星)的演化歷史。因此我們可能可以提出一個合理的微衛星演化模型。基於這個模型，我們也可以利用電腦去模擬微衛星的演化。模擬的結果與實際觀察到的資料的一致性便可用來評估我們所提出模型的可靠度。

It has been well documented that more than half of the human genome is composed of repetitive DNA, and most of these repetitive DNA is made up of transposable elements (jumping genes), including transposons and retrotransposons. The primate specific retrotransposon, Alu element, along with another kind of retrotransposon, LINE 1 (long interspersed nucleotide element 1, L1), account for approximately 27% of the human genome. Traditionally, these transposable elements were thought to be useless ‘junk DNA’ or ‘selfish DNA’. However, an unusual cluster of positional proximity of Alu elements and several primate specific microRNA genes was recently found in human chromosome 19. This cluster was named as C19MC (chromosome 19 microRNA cluster). We hypothesized that this unusual fragment was derived from a serious of duplication events. Although the function of these primate specific microRNAs is still unknown, it is reasonable to speculate that the emergence of primate species might correlate with the expansion of C19MC sequences. It is likely that the expansion of C19MC was attributed to Alu-mediated tandem duplication events. We therefore are interested in analyzing the evolutionary history of C19MC. By identifying each historical duplication event, we might be able to propose a possible model for the expansion of C19MC. Our study might also shed light on the interaction between transposable elements and microRNA in primate genomes. Further, we would like to investigate whether we could find similar clusters (and similar mechanisms) in genomes of other model organisms. The second part of our proposal is to study the evolution of embedded simple repeats (microsatellites) in primate LINE 1 elements. It was recognized that microsatellites have extremely high mutation rates. Therefore it is usually not easy to identify orthologous microsatellites between distant species pairs. Because the number of identified orthologous microsatellites is limited, researchers usually could not obtain sufficient information to model the evolution of microsatellites. Fortunately, we found that some LINE 1 elements embedded simple repeats at a certain location in our previous works. The length and sequences of these simple repeats vary widely among LINE 1 elements. Since all the LINE 1 elements could be well aligned, we could construct a reliable evolutionary history for all the LINE 1 elements. This evolutionary history could be properly applied to the abundant embedded simple repeats (microsatellites). We therefore might be able to propose a reasonable model for the evolution of microsatellites. Based on the proposed model, we could simulate the evolution of microsatellites. The consistency between simulation results and the observed data could be used to examine how reliable the proposed model is.