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1、Lesson Five,Discovering the Chemical Nature of the Gene,Purine: 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 deoxyribo
2、se(脫氧核糖),double helix:雙螺旋The three-dimensional structure of double-stranded DNA.,,DNA polymerase: 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 molecu
3、le.,Okazaki fragment: 岡崎片段A short sequence of DNA that is the primary product of DNA polymerase during DNA replication.在DNA雙鏈進行半保留復制時,在復制點附近新合成的與親代DNA鏈互補的DNA片段。是岡崎令治等(1966)首先發(fā)現(xiàn)的。,semiconservative replication:半保留復制T
4、he 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 th
5、at a large class of gene exist in which each gene controls the synthesis or activity of but a single enzyme.,認為一個基因僅僅參與一個酶的生成,并決定該酶的特異性和影響表型。G.W.Bea-dle和E.L.Tatum在1941年發(fā)表了鏈孢霉中生化反應遺傳控制的研究;進而使應用各種生化突變型對基因作用的研究有了發(fā)展。Beadle在1
6、945年總結(jié)了這些結(jié)果,提出了一個基因一個酶的假說。以后發(fā)現(xiàn),不僅鏈孢霉,而且細菌和酵母菌等各種生物由于生化突變都會引起特定酶的缺損,從而導致了特定的代謝反應阻滯,這進一步證明了這個假說的正確性。但是有些酶是由不同的多肽鏈特異地聚合起來才會呈現(xiàn)有活性,也有一個基因所決定的同樣多肽鏈是兩種或兩種以上不同酶的組成成分。此外,有的基因能決定具有兩種或兩種以上作用的酶,也有幾個基因所決定的多肽鏈通過聚合才能發(fā)揮作用。隨著酶學、蛋白質(zhì)化學的進展、
7、遺傳學方法的進步,進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密對應的關(guān)系基礎(chǔ)上的。表示這種對應關(guān)系的學說就是一個基因一條多肽鏈假說。,one-gene-one-polypeptide (多肽)hypothesis: The hypothesis that a large class of genes exist in which each gene controls the synthesis of a single pol
8、ypeptide. The polypeptide may function independently or as a subunit of a more complex protein,Genes code for particular proteinsThe first scientist to investigate the question of how genes affect phenotype was Sir Ar
9、chibald Garrod, whose studies of alkaptonuria (尿黑酸癥)implied a relationship between genes and enzymes.Archibald Garrod是第一個研究基因是如何影響表型的科學家,他對尿黑酸癥的研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),患者由于體
10、內(nèi)缺乏分解尿黑酸(alkapton)的酶,因此,排出的尿呈深紅色。這是首次將一個遺傳性狀和一個蛋白質(zhì)的活性進行了鏈接。,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
11、, Beadle 和Ephrussi在對果蠅眼睛顏色的研究發(fā)現(xiàn)特殊基因與相關(guān)反應的生物合成有關(guān)。,Next, in a series of classic experiments on the effects of mutations in the bread mold Neurospora crassa,Beadle and Tatum explored the one-gene-one-enzyme hypothesis—the i
12、dea that each gene codes for a particular enzyme.接下來,Beadle和Tatum進行了一系列面包霉粗糙脈孢菌的突變試驗, 得出一個基因一個酶的假說。,Their work paved the way for other scientists to elucidate the precise ways in which enzymes affect complex metabolic
13、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雜的新陳代謝途徑。,In 1949, in research on the role of hemoglobin(血紅素)in sickle(鐮刀) cell anemia(貧血癥), Linus Pauling helped refine the one-gene-one-enzyme hypothesis into the one-gene-one-p
14、olypeptide hypothesis. 1949年,Linus Pauling對鐮刀狀細胞貧血癥血紅素的研究將一個基因一個酶的假說上升為一個基因一個多肽假說。,2. The search for the chemistry and molecular structure of nucleic acidsNuclei acids, originally isolated by Johann Miescher in
15、1871, was identified as a prime constituent of chromosomes through 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,二十世紀早期Feulgen用紅色染料染色法證實核酸是染色體組最基本的成分。,Frede
16、rick Griffith’s experiments with the Rough and Smooth stains of pneumococci showed that as yet unknown material from one set of bacterial could alter the physical traits of a second set. Frederick Griffith對粗糙和光滑的肺炎雙
17、球菌實驗表明,不確定的某種物質(zhì)可以從一組細菌轉(zhuǎn)移到另一種細菌中并能改變另一種細菌的物理屬性。,In the 1940s the team of Avery, MacLeod, and McCarty showed that this unknown material was DNA.二十世紀四十年代,Avery, MacLeod和McCarty研究小組確認該物質(zhì)為DNA。,1935年,美國洛克菲勒學院的Osvald T. Avery
18、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成分。1944年發(fā)表報告說,已將該物質(zhì)分離出,活性極強。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 whic
19、h was attached to a sugar molecule and a phosphate group-a combination Levene termed a nucleotide幾乎同時, P.A.Levene 發(fā)現(xiàn)DNA包含四種含氮堿基,每個堿基和磷酸分子分別連接在糖分子上,Levene把這個復合物稱為核苷酸。,P.A.Levene (1869,2,25俄國Sasor-1940,9,6美國紐約)1891年畢業(yè)于圣彼
20、得堡帝國軍事醫(yī)學院, 醫(yī)學博士, 與其老師A.Kssel及同學W.Jones 一起弄清了弄清了核酸的基本化學結(jié)構(gòu),證實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),核糖有2種(核糖與脫氧核糖),Disagreement over whether DNA could carry complex genetic information was ended in the e
21、arly 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.二十世紀五十年代初期,關(guān)于DNA能否負載復雜的遺傳信息的分歧結(jié)束, Martha Chase and Alfred Hershey,通過對大
22、腸桿菌實驗發(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 每個核苷酸都含有一個五碳、脫氧核糖,分別連接4個堿基,即:腺嘌呤,鳥嘌呤,胞嘧啶,胸腺嘧啶。,Adenine and
23、 guanine molecules are double-ring structures called purines, while 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 bas
24、e 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 sugar of the next nucleoside in the chain. This phosphate bonding creates
25、a sugar-phosphate backbone.堿基連接糖稱核苷。磷酸鍵形成糖-磷酸骨架。,Chargaff’s 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 r
26、atios of A to 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 195
27、0s, researchers looking for the structure of DNA drew upon Chargaff’s insight, Levene’s ideas on DNA 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 的觀點和Levene的組成理論以及其他兩個線索。,One was th
28、e 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 structure with distance between the coils, taken
29、 by Franklin and Wilkins.一個是Linus Pauling的假設,DNA可能具有螺旋的結(jié)構(gòu),通過氫鍵連接。另一個是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 la
30、dder -like molecule with two outer sugar phosphate chains and rungs(梯子的橫檔,梯級)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,核苷對形成梯子的橫檔。,Paired nucleotide, which always occur as A-
31、T or G-C, are linked by hydrogen bonds. Watson and Crick also proposed that genetic information is encoded by the sequence of base pairs along the DNA molecule. A和T或者G和C配對,他們之間通過H鍵相連。Watson和Crick還提出遺傳信息是由DNA分子的堿基對序列編碼的
32、。,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 Crick 假設DNA是以
33、解開拉鏈方式自我復制的,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、互補鏈。,This model of semiconserv
34、ative replication-conservative because each new molecule has one half of the former parent molecule-was later confirmed by the work of Meselson and Stahl. 此即為半保留復制,保留是因為每一新分子含有父母分子的一半,隨后這一假設被Meselson 和 Stahl 所證實。,In E.
35、coli DNA replication begins with the formation of a bubblelike structure on the circular chromosome that is produced by replication forks.大腸桿菌DNA復制開始時在環(huán)形染色體上形成泡狀結(jié)構(gòu),那是由復制叉產(chǎn)生的。,Studies of bacterial DNA replication have s
36、hown that a growing DNA chain lengthens only in the 5’ to 3’ direction(from the 5’ carbon of one sugar to the 3’ carbon of the next).對細菌DNA復制的研究表明,鏈生長方向由5′向3′端,,The leading strand is synthesized continuously ,while the
37、 lagging strand is synthesized in short stretches known as Okazaki fragments. 前導鏈連續(xù)生成,后隨鏈由岡崎片段組成.,The enzyme DNA polymerase links free nucleotides as they line up(排成行)on the template formed by the original strand of th
38、e parent molecule.當核苷在親本分子原始鏈形成的模板上排成行時,DNA聚合酶把這些自由的核苷連接到一起。,In eukaryotes DNA replication follows the same general principles as in prokaryotes . On the long DNA molecules replication proceeds(in two directions at onc
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