解析原核生物基因轉錄之驟發現象

Abstract

基因表現是主要包含兩個步驟: 轉錄和轉譯。首先，RNA聚合酶必須先結合到DNA中的特定序列，才能啟始基因轉錄。然而目前對於RNA聚合酶透過何種機制去尋找到特定的結合位置，仍然是個未解的謎。在過去幾十年來，有許多關於RNA聚合酶的移動機制的動力模型被提出，然而在生物體中的實際現象，仍尚待更進一步研究。 本篇論文目的在於研究RNA聚合酶的移動行為會如何影響基因轉錄的現象。我們透過建立一個RNA聚合酶在DNA序列上做隨機運動的模型，使用電腦模擬的方式來探討在原核生物中基因驟發性轉錄的特性。透過使用蒙地卡羅模擬法，來驗證我們的模型並和實際生物實驗做比較。 我們的實驗結果顯示，在適當的參數假設下，模擬結果相當接近一些實際的生物實驗，我們的理論模型和模擬結果，提出一些驟發性轉錄現象的可能原因，並引入了一些參數假設，尚待在未來生物實驗中驗證所代表實際上的生物意義。

Gene expression consists of two main steps: transcription and translation. It origins from the binding of RNA polymerases to their target sites on DNA sequences. The mechanism how RNA polymerases locate their target sites remains a puzzling mystery. It affects almost all aspects of biology. Over the past few decades, many related studies have been made on the regulation of gene expression. Although several models have been proposed and demonstrated for the mechanism, many details of the elementary steps of gene transcription in vivo are still open for debate. This thesis aims to explain how the motion of RNA polymerases affects gene transcription dynamics and the transcriptional bursting. We introduce a random walk model for the motion of RNA polymerases along DNA during the search of target locations and the transcription process. In order to verify our model, we apply Monte Carlo simulation and simplified statistical computation to compare our prediction to prior experimental data. The findings suggest that under proper assumptions, our model is able to explain the transcriptional bursting phenomenon, and computer simulations are consistent with prior experimental data. Our results also suggest some parameters which await experiments to justify their biological significances.