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研究生： 陳大元
Ta-Yuan Chen
論文名稱： 人類病源體中的攝取訊號序列分析
DNA Uptake Signal Sequence in Human Pathogens
指導教授： 李弘謙
Hoong-Chien Lee
口試委員:
學位類別： 博士
Doctor
系所名稱： 理學院 - 物理學系
Department of Physics
畢業學年度： 93
語文別： 英文
論文頁數： 67
中文關鍵詞： 攝取訊號序列 、嗜血桿菌
外文關鍵詞： Haemophilus, Uptake Signal Sequence
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    • 1.8 M長的嗜血桿菌（Haemophilus influenzae）基因組帶有1471個攝取訊號序列(uptake signal sequence USS) 。完整的嗜血桿菌攝取訊號序列為一個29 base長的序列，當中有9 base長的序列（AAGTGCGGT）是完全保守的。嗜血桿菌中有66%的攝取訊號序列嵌入在1738個已知或猜測的基因中。攝取訊號序列出現在嗜血桿菌基因組中的頻率為一個9 base長序列平均出現在嗜血桿菌基因組頻率的200倍。完整的攝取訊號序列總共大約佔了嗜血桿菌基因組長度的2.4%。基因組裡要存在這麼多的攝取訊號序列必須在維持細胞正常運作及攝取功能的演化上達到一定程度上的利益平衡。在此我們就從擁有這些攝取訊號序列所需付出的代價作定性的研究。我們分析結果是，細菌以各種可能的方法儘量減低它們擁有眾多攝取訊號序列所付出的代價。第二部分的分析之中，我們想要知道攝取訊號序列的演化是否穩定。嗜血桿菌跟巴斯德桿菌的共同祖先出現在兩億七千萬年前。在比對攝取訊號序列之後，我們發現有大約百分之六十的攝取訊號序列是屬於同源的序列，所以我們推測攝取訊號序列的演化是穩定而且緩慢的。

    The 1.8 Mbp genome of Haemophilus influenzae carries 1471 copies of its DNA uptake signal sequence (USS), a 29 bases long oligonucleotide including a 100% conserved 9-base core, AAGTGCGGT, 66% of the which are embedded in the 1738 known and putative genes of the genome. The frequency of occurrence of the 9-base (core) USS is about 200 times statistical expectation. Together with its flanks, the USS in H. influenzae take up 2.4% of the otherwise streamlined genome. The embedding of so many USS in the genome is a penalty to the organism that must be balance by benefit to the organism derived from maintaining and evolving the uptake system. As a first step to understanding this balance we want to characterize and determine this cost. We find that at every possible instance the genome tried to minimize the cost. In the second part, we want to characterize the stability of USS evolution. H. influenzae and P. multocida have a common ancestor 270 million years ago. We find that about 60% USSs are homologs and conjecture that the evolution of USS has been stable and slow.

    Chapter 1 Introduction 1 1-1 Bacteria 1 1-2 Natural competence 5 1-3 Uptake signal sequence (USS) 7 1-4 Questions 10 Chapter 2 Cost Analysis 11 2-1 Basic information of H.I. and N.M. 11 2-2 Distribution of USS in coding and non-coding regions 19 2-3 Compare the genes with USS and without USS 23 2-4 Homologous proteins with UEP and without UEP 28 2-5 Segment of UEP in protein 33 Chapter 3 Evolution 46 3-1 USS frequency in H. influenzae and P. multocida 46 3-2 Compare USS homology by position in the gene 50 3-3 Confirmation of USS homology by sequence alignments 54 3-4 USS homology in other species 56 Chapter 4 Summary and discussions 58 References 61 Appendix A FASTA formate 63 Appendix B BLOSOM62 65 Appendix C PAM30 66 Appendix D Genetic code 67

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