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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/30936

Title: 血基質生合成途徑酵素之親緣關係及演化分析
Phylogenetic and Evolutionary Study of Heme Biosynthesis Pathway
Authors: Zong-Ye You
游宗燁
Contributors: NTOU:Institute of Bioscience and Biotechnology
國立臺灣海洋大學:生物科技研究所
Keywords: 血基質
Heme
Date: 2012
Issue Date: 2012-04-16T03:13:17Z
Abstract: 摘要 Heme為一個具有Tetrapyrrole結構的物質,在真核生物、細菌及古細菌中都有被發現,主要作用為電子傳遞、光合成反應及酵素催化,已知在Hemoglobin、Myoglobin、Catalases、Peroxiases、Cytochrome P450及O2、NO接受器蛋白都有Heme的存在。在真核生物與原核生物都有發現Heme的生合成,而ALAS的isoform (ALAS2)為專一表現在紅血球,顯示Heme合成與血球發育息息相關,因此本論文探討Heme合成途徑的八個酵素在動物界分佈狀況與親緣關係,並同時觀察Heme的生合成pathway是否有演化壓力存在。 本研究是藉由搜集基因資料庫中動物界各物種的Heme合成途徑中八種酵素的蛋白質序列(5'-aminolevulinate synthase、Aminolevulinic Acid Dehydratase、Porphobilingoen Deaminase、Uroporphyrinogen III Synthase、Uroporphyrinogen Decarboxylase、Coproporphyrinogen Oxidase、Protoporphyrinogen Oxidase、Ferrochelatase),利用這些序列來建構親緣關係樹。我們從基因親緣關係樹發現各基因主要可分成脊椎動物和節肢動物兩大群,脊椎動物中直接劃分成五個分化枝,分別是哺乳類、魚類、兩棲類、爬蟲、鳥類,這種分群具有高統計值(bootstrap values),可知其分群在統計上具有相當的可信程度。我們也分析人類、小鼠、斑馬魚、果蠅的八種酵素在染色體的座落位置和相鄰基因,僅發現人類、小鼠的相鄰基因較為相似。 我們同時探討Heme合成途徑八種酵素的基因序列的演化壓力,我們發現演化壓力為負向演化力量(Negative selection或Purifying selection),也就是非同義鹼基替代率與同義鹼基替代率的比值小於1(dN/dS <1),數值介於0.05到0.16之間,其中以Uroporphyrinogen III Synthase與Protoporphyrinogen Oxidase兩種基因dN/dS數值較高。 另外,我們在魚類的5'-aminolevulinate synthase 2、Coproporphyrinogen Oxidase和節肢動物的Aminolevulinic Acid Dehydratase,發現具有正向演化(Positive selection或Adaptive selection)的可能性,並進一步偵測得知有一些胺基酸具有Positive selection的可能,分析這些胺基酸在蛋白質結構上的相對位置,發現有些胺基酸位於酵素活化區內,也有位於蛋白質單體間的介面處,其中有兩個胺基酸的突變與人類遺傳疾病有關。
Abstract Heme, a tetrapyroole compound, can be found in proteins such as hemoglobin, myoglobin, catalases, peroxiases, cytochrome P450, O2 re-ceptors and NO receptors. Heme is involved in diverse biological processes including electron transport, photosynthesis, and enzyme reactions. Heme synthesis were found in eukaryotes and prokaryotes, while the ALAS isoform (ALAS2) is expressed in red blood cells specifically. It suggests heme synthesis and blood cell development are close-related. In this study, we investigated the distribution and phylogentics of eight enzymes involved in heme biosynthesis pathway in animal kingdom. Moreover, we also studies if there were any evolutionary pressure imposed on the heme biosynthesis pathway. In this research we collected amino acid sequences of eight proteins responsible for the bio-synthesis of heme and constructed the phylogenetic trees for these eight proteins from the animal kingdom. These eight proteins are 5'-aminolevulinate synthase, Aminolevulinic Acid Dehydratase, Porphobilingoen Deaminase, Uroporphyrinogen III Synthase, Uroporphyrinogen Decarboxylase, Coproporphyrinogen Oxidase, Protoporphyrinogen Oxidase and Ferrochelatase. We discovered that proteins from vertebrate and arthropod lineages form two major clusters in the phylogenetic trees, and, from the vertebrate branch, we could infer the evolutionary relationships among mammals, fish, amphibians, reptiles and birds lineages. We also analyzed the gene linkages by investigating the neighboring genes and found only human and mouse have similar order of genes involved in heme biosynthesis. We also found all eight genes of all lineages are under high negative selection pressure, that is, omega value (dN/dS) is smaller than 1, with values ranging from 0.05 to 0.16. dN/dS values of Uroporphyrinogen III Synthase and Protoporphyrinogen Oxidase genes are higher than those of other genes in heme-biosynthesis pathway. However, by implementing likelihood ratio test, coding sequences of 5'-aminolevulinate synthase 2 and Coproporphyrinogen Oxidase of fish lineage together with coding sequence of Aminolevulinic Acid Dehydratase of arthropod lineage are under the pressure of positive selection. Several amino acids under apparent positive selection can be interpreted from the protein three-dimensional point of view. Some are located in active site region and others in the interface of biologically functional homodimer. Moreover, two amino acids were reported to cause human hereditary disease of blood.
URI: http://ethesys.lib.ntou.edu.tw/cdrfb3/record/#G0M98360040
http://ntour.ntou.edu.tw/handle/987654321/30936
Appears in Collections:[生命科學暨生物科技學系] 博碩士論文

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