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1、Lesson FiveDiscovering the Chemical Nature of the GenePurine: 嘌呤adenine:腺嘌呤guanine:鳥嘌呤 Pyrimidine:嘧啶cytosine:胞嘧啶thymine:胸腺嘧啶uracil:尿嘧啶nucleoside:核苷A purine or pyrimidine base attached to ribose(核糖) or deoxyribose(脫氧核糖)double helix:雙螺旋The three-dimensional structure of double-stranded DNA.DNA polymer

2、ase: DNA聚合酶An enzyme that brings new DNA triphosphate(三磷酸鹽) nucleotides(核苷) into position for bonding on another DNA molecule.Okazaki fragment: 岡崎片段A short sequence of DNA that is the primary product of DNA polymerase during DNA replication.在DNA雙鏈進(jìn)行半保留復(fù)制時(shí),在復(fù)制點(diǎn)附近新合成的與親代DNA鏈互補(bǔ)的DNA片段。是岡崎令治等(1966)首先發(fā)現(xiàn)的。

3、semiconservative replication:半保留復(fù)制The method of replication of DNA in which the molecule divides longitudinally(縱向地), each half being conserved and acting as a template for the formation of a new strand.one-gene-one-enzyme hypothesis: The hypothesis that a large class of gene exist in which each gen

4、e controls the synthesis or activity of but a single enzyme.認(rèn)為一個(gè)基因僅僅參與一個(gè)酶的生成,并決定該酶的特異認(rèn)為一個(gè)基因僅僅參與一個(gè)酶的生成,并決定該酶的特異性和影響表型。性和影響表型。G.W.Bea-dleG.W.Bea-dle和和E.L.TatumE.L.Tatum在在19411941年發(fā)表了年發(fā)表了鏈孢霉中生化反應(yīng)遺傳控制的研究;進(jìn)而使應(yīng)用各種生化鏈孢霉中生化反應(yīng)遺傳控制的研究;進(jìn)而使應(yīng)用各種生化突變型對(duì)基因作用的研究有了發(fā)展。突變型對(duì)基因作用的研究有了發(fā)展。BeadleBeadle在在19451945年總結(jié)年總結(jié)了這些結(jié)果,

5、提出了一個(gè)基因一個(gè)酶的假說。以后發(fā)現(xiàn),了這些結(jié)果,提出了一個(gè)基因一個(gè)酶的假說。以后發(fā)現(xiàn),不僅鏈孢霉,而且細(xì)菌和酵母菌等各種生物由于生化突變不僅鏈孢霉,而且細(xì)菌和酵母菌等各種生物由于生化突變都會(huì)引起特定酶的缺損,從而導(dǎo)致了特定的代謝反應(yīng)阻滯,都會(huì)引起特定酶的缺損,從而導(dǎo)致了特定的代謝反應(yīng)阻滯,這進(jìn)一步證明了這個(gè)假說的正確性。但是有些酶是由不同這進(jìn)一步證明了這個(gè)假說的正確性。但是有些酶是由不同的多肽鏈特異地聚合起來才會(huì)呈現(xiàn)有活性,也有一個(gè)基因的多肽鏈特異地聚合起來才會(huì)呈現(xiàn)有活性,也有一個(gè)基因所決定的同樣多肽鏈?zhǔn)莾煞N或兩種以上不同酶的組成成分。所決定的同樣多肽鏈?zhǔn)莾煞N或兩種以上不同酶的組成成分。此外

6、,有的基因能決定具有兩種或兩種以上作用的酶,也此外,有的基因能決定具有兩種或兩種以上作用的酶,也有幾個(gè)基因所決定的多肽鏈通過聚合才能發(fā)揮作用。隨著有幾個(gè)基因所決定的多肽鏈通過聚合才能發(fā)揮作用。隨著酶學(xué)、蛋白質(zhì)化學(xué)的進(jìn)展、遺傳學(xué)方法的進(jìn)步,進(jìn)一步弄酶學(xué)、蛋白質(zhì)化學(xué)的進(jìn)展、遺傳學(xué)方法的進(jìn)步,進(jìn)一步弄清楚了基因與酶的關(guān)系是建立在基因與多肽鏈嚴(yán)密對(duì)應(yīng)的清楚了基因與酶的關(guān)系是建立在基因與多肽鏈嚴(yán)密對(duì)應(yīng)的關(guān)系基礎(chǔ)上的。表示這種對(duì)應(yīng)關(guān)系的學(xué)說就是一個(gè)基因一關(guān)系基礎(chǔ)上的。表示這種對(duì)應(yīng)關(guān)系的學(xué)說就是一個(gè)基因一條多肽鏈假說。條多肽鏈假說。 one-gene-one-polypeptide (多肽)hypothes

7、is: The hypothesis that a large class of genes exist in which each gene controls the synthesis of a single polypeptide. The polypeptide may function independently or as a subunit of a more complex protein1.Genes code for particular proteinsThe first scientist to investigate the question of how genes

8、 affect phenotype was Sir Archibald Garrod, whose studies of alkaptonuria (尿黑酸癥尿黑酸癥)implied a relationship between genes and enzymes.Archibald GarrodArchibald Garrod是第一個(gè)研究基因是如是第一個(gè)研究基因是如何影響表型的科學(xué)家,他對(duì)尿黑酸癥的研何影響表型的科學(xué)家,他對(duì)尿黑酸癥的研究揭示了基因與酶之間的關(guān)系。究揭示了基因與酶之間的關(guān)系。 1902年,Archibold Garrod發(fā)現(xiàn)了一種人類遺傳疾病尿黑酸癥(alkaptonuria

9、),患者由于體內(nèi)缺乏分解尿黑酸(alkapton)的酶,因此,排出的尿呈深紅色。這是首次將一個(gè)遺傳性狀和一個(gè)蛋白質(zhì)的活性進(jìn)行了鏈接。Thirty years later Beadle and Ephrussi showed a relationship between particular genes and biosynthetic reactions responsible for eye color in fruit flies.三十年后, Beadle 和Ephrussi在對(duì)果蠅眼睛顏色的研究發(fā)現(xiàn)特殊基因與相關(guān)反應(yīng)的生物合成有關(guān)。Next, in a series of classic

10、 experiments on the effects of mutations in the bread mold Neurospora crassa,Beadle and Tatum explored the one-gene-one-enzyme hypothesisthe idea that each gene codes for a particular enzyme.接下來,Beadle和Tatum進(jìn)行了一系列面包霉粗糙脈孢菌的突變?cè)囼?yàn), 得出一個(gè)基因一個(gè)酶的假說。 Their work paved the way for other scientists to elucidate

11、 the precise ways in which enzymes affect complex metabolic pathways. 他們的工作為其他工作者鋪平了道路,即精確地闡明了酶影響了復(fù)雜的新陳代謝途徑。 In 1949, in research on the role of hemoglobin(血紅素血紅素)in sickle(鐮刀鐮刀) cell anemia(貧血癥貧血癥), Linus Pauling helped refine the one-gene-one-enzyme hypothesis into the one-gene-one-polypeptide hyp

12、othesis. 1949年,年,Linus Pauling對(duì)鐮刀狀細(xì)胞貧血癥血對(duì)鐮刀狀細(xì)胞貧血癥血紅素的研究將一個(gè)基因一個(gè)酶的假說上升為一紅素的研究將一個(gè)基因一個(gè)酶的假說上升為一個(gè)基因一個(gè)多肽假說。個(gè)基因一個(gè)多肽假說。2. The search for the chemistry and molecular structure of nucleic acidsNuclei acids, originally isolated by Johann Miescher in 1871, was identified as a prime constituent of chromosomes thr

13、ough the use of the red-staining method developed by Feulgen in the early 1900s.核酸最初是由Johann Miescher于1871 年分離成功,二十世紀(jì)早期Feulgen用紅色染料染色法證實(shí)核酸是染色體組最基本的成分。 Frederick Griffiths experiments with the Rough and Smooth stains of pneumococci showed that as yet unknown material from one set of bacterial could a

14、lter the physical traits of a second set. Frederick Griffith對(duì)粗糙和光滑的對(duì)粗糙和光滑的肺炎雙球菌肺炎雙球菌實(shí)驗(yàn)表明,不確定的某種物質(zhì)可以從一組細(xì)菌實(shí)驗(yàn)表明,不確定的某種物質(zhì)可以從一組細(xì)菌轉(zhuǎn)移到另一種細(xì)菌中并能改變另一種細(xì)菌的物轉(zhuǎn)移到另一種細(xì)菌中并能改變另一種細(xì)菌的物理屬性。理屬性。 In the 1940s the team of Avery, MacLeod, and McCarty showed that this unknown material was DNA.二十世紀(jì)四十年代,Avery, MacLeod和McCarty研

15、究小組確認(rèn)該物質(zhì)為DNA。1935年,美國洛克菲勒學(xué)院的Osvald T. Avery和Colin M.MacLeod及Maclyn McCarty開始試圖純化能把R品系變成S品系的轉(zhuǎn)化因子并鑒定其化學(xué)成分。1944年發(fā)表報(bào)告說,已將該物質(zhì)分離出,活性極強(qiáng)。用蛋白酶或核酸酶處理不影響其轉(zhuǎn)化能力,用DNA酶處理轉(zhuǎn)化能力消失。 At about the same time P.A.Levene discovered that DNA contained four nitrogenous bases, each of which was attached to a sugar molecule an

16、d a phosphate group-a combination Levene termed a nucleotide幾乎同時(shí), P.A.Levene 發(fā)現(xiàn)DNA包含四種含氮堿基,每個(gè)堿基和磷酸分子分別連接在糖分子上,Levene把這個(gè)復(fù)合物稱為核苷酸。 P.A.Levene (1869,2,25俄國Sasor-1940,9,6美國紐約)1891年畢業(yè)于圣彼得堡帝國軍事醫(yī)學(xué)院, 醫(yī)學(xué)博士, 與其老師A.Kssel及同學(xué)W.Jones 一起弄清了弄清了核酸的基本化學(xué)結(jié)構(gòu),證實(shí)核酸是由許多核苷酸組成的大分子。核苷酸是由堿基、核糖和磷酸構(gòu)成。其中堿基有4種(腺瞟呤、鳥瞟呤、胞嘧啶和胸腺嘧啶),核糖

17、有2種(核糖與脫氧核糖) Disagreement over whether DNA could carry complex genetic information was ended in the early 1950s by Martha Chase and Alfred Hershey, whose work with E.coli showed clearly that DNA, and not protein, is the bearer of genetic information.二十世紀(jì)五十年代初期,關(guān)于DNA能否負(fù)載復(fù)雜的遺傳信息的分歧結(jié)束, Martha Chase and

18、 Alfred Hershey,通過對(duì)大腸桿菌實(shí)驗(yàn)發(fā)現(xiàn),遺傳物質(zhì)是DNA,而不是蛋白質(zhì)。 Each DNA nucleotide contains a five-carbon sugar, deoxyribose, attached to one of four bases: adenine, guanine, cytosine, or thymine 每個(gè)核苷酸都含有一個(gè)五碳、脫氧核糖,分別連接4個(gè)堿基,即:腺嘌呤,鳥嘌呤,胞嘧啶,胸腺嘧啶。 Adenine and guanine molecules are double-ring structures called purines, wh

19、ile cytosine and thymine are single-ring structures called pyrimidines.腺嘌呤和鳥嘌呤分子是雙環(huán)結(jié)構(gòu)叫嘌呤,胞嘧啶和胸腺嘧啶是單環(huán)結(jié)構(gòu)叫嘧啶。 腺嘌呤鳥嘌呤胞嘧啶胸腺嘧啶 The molecule made up of a base plus a sugar is termed a nucleoside. In each molecule of DNA a phosphate group links the five-carbon sugar of one nucleoside to the five-carbon suga

20、r of the next nucleoside in the chain. This phosphate bonding creates a sugar-phosphate backbone.堿基連接糖稱核苷。磷酸鍵形成糖-磷酸骨架。 Chargaffs rules describe the fact that(1) the amount of adenine is equal to the amount of thymine in DNA, with amount of cytosine equal to that of guanine, and (2)the ratios of A to

21、 T and of C to G vary with different species. Chargaff定律說明(1)DNA中腺嘌呤與胸腺嘧啶,胞嘧啶與鳥嘌呤數(shù)量相等;(2)腺嘌呤與胸腺嘧啶,胞嘧啶與鳥嘌呤的比例隨物種不同而不同。 3. The research race for the molecular structure of DNAIn the late 1940s and early 1950s, researchers looking for the structure of DNA drew upon Chargaffs insight, Levenes ideas on D

22、NA components, and two other lines of evidence.40年代末50年代初,研究者在尋求DNA結(jié)構(gòu)過程中,借鑒了Chargaff 的觀點(diǎn)和Levene的組成理論以及其他兩個(gè)線索。 One was the suggestion of Linus Pauling that DNA might have a helical structure held in place by hydrogen bonds, and the other was X-ray diffraction photos of DNA, showing a helical structur

23、e with distance between the coils, taken by Franklin and Wilkins.一個(gè)是Linus Pauling的假設(shè),DNA可能具有螺旋的結(jié)構(gòu),通過氫鍵連接。另一個(gè)是DNA的X射線-衍射圖片,圖片顯示卷曲間間隔呈螺旋結(jié)構(gòu),圖片由Franklin and Wilkins提供。 Based on this information Watson and Crick proposed the double helix model of DNA-a twisted ladder -like molecule with two outer sugar p

24、hosphate chains and rungs(梯子的橫檔,梯級(jí))formed by nucleotide pairs.基于這些信息,Watson 和 Crick提出了雙螺旋結(jié)構(gòu)模型,即DNA是一盤繞成梯子形狀的分子,外部是兩條糖磷酸鏈,核苷對(duì)形成梯子的橫檔。 Paired nucleotide, which always occur as A-T or G-C, are linked by hydrogen bonds. Watson and Crick also proposed that genetic information is encoded by the sequence o

25、f base pairs along the DNA molecule. A和T或者G和C配對(duì),他們之間通過H鍵相連。Watson和Crick還提出遺傳信息是由DNA分子的堿基對(duì)序列編碼的。4. How DNA replicatesIn their model of DNA structure and function, Watson and Crick hypothesized that DNA replicates itself by “unzipping” along the hydrogen bonds joining A to T and C to G. Watson and Cri

26、ck 假設(shè)DNA是以解開拉鏈方式自我復(fù)制的,即A和T以及C和G之間的氫鍵斷裂。This process would produce two opposite halves that could then serve as templates for the construction of new, complementary strands.這一過程將產(chǎn)生兩條相反鏈,分別以其為模板生成新的、互補(bǔ)鏈。This model of semiconservative replication-conservative because each new molecule has one half of the former parent molecule-was later confirmed by the work of Meselson and Stahl. 此即為半保留復(fù)制,保留是因?yàn)槊恳恍路肿雍懈改阜肿拥囊话?,隨后這一假設(shè)被Meselson 和 Stahl 所證實(shí)。In E.coli DNA replication begins with the formation of a bubblelike structure on the circular chromosome that is produced by r

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