1、Lesson Five,Discovering the Chemical Nature of the Gene,Purine: 嘌呤adenine:腺嘌呤guanine:鸟嘌呤 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(脱氧核糖),double helix:双螺旋The three-dimensional structure of double-stranded DNA.,DNA po
2、lymerase: DNA聚合酶An enzyme that brings new DNA triphosphate(三磷酸盐) nucleotides(核苷) into position for bonding on another DNA molecule.,Okazaki fragment: 冈崎片段A short sequence of DNA that is the primary product of DNA polymerase during DNA replication.在DNA双链进行半保留复制时，在复制点附近新合成的与亲代DNA链互补的DNA片段。是冈崎令治等（1966）
3、首先发现的。,semiconservative replication:半保留复制The method of replication of DNA in which the molecule divides longitudinally(纵向地), 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
4、each gene controls the synthesis or activity of but a single enzyme.,认为一个基因仅仅参与一个酶的生成，并决定该酶的特异性和影响表型。G.W.Bea-dle和E.L.Tatum在1941年发表了链孢霉中生化反应遗传控制的研究；进而使应用各种生化突变型对基因作用的研究有了发展。Beadle在1945年总结了这些结果，提出了一个基因一个酶的假说。以后发现，不仅链孢霉，而且细菌和酵母菌等各种生物由于生化突变都会引起特定酶的缺损，从而导致了特定的代谢反应阻滞，这进一步证明了这个假说的正确性。但是有些酶是由不同的多肽链特异地聚合起来才会
5、呈现有活性，也有一个基因所决定的同样多肽链是两种或两种以上不同酶的组成成分。此外，有的基因能决定具有两种或两种以上作用的酶，也有几个基因所决定的多肽链通过聚合才能发挥作用。随着酶学、蛋白质化学的进展、遗传学方法的进步，进一步弄清楚了基因与酶的关系是建立在基因与多肽链严密对应的关系基础上的。表示这种对应关系的学说就是一个基因一条多肽链假说。,one-gene-one-polypeptide (多肽)hypothesis: The hypothesis that a large class of genes exist in which each gene controls the synthes
6、is of a single polypeptide. 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 Archibald Garrod, whose studies of alkaptonuria (尿黑酸症)implied a rel
7、ationship between genes and enzymes.Archibald Garrod是第一个研究基因是如何影响表型的科学家，他对尿黑酸症的研究揭示了基因与酶之间的关系。,1902年，Archibold Garrod发现了一种人类遗传疾病尿黑酸症(alkaptonuria)，患者由于体内缺乏分解尿黑酸(alkapton)的酶，因此，排出的尿呈深红色。这是首次将一个遗传性状和一个蛋白质的活性进行了链接。,Thirty years later Beadle and Ephrussi showed a relationship between particular genes an
8、d biosynthetic reactions responsible for eye color in fruit flies.三十年后, Beadle 和Ephrussi在对果蝇眼睛颜色的研究发现特殊基因与相关反应的生物合成有关。,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 hypothesisthe idea that ea
9、ch gene codes for a particular enzyme.接下来，Beadle和Tatum进行了一系列面包霉粗糙脉孢菌的突变试验, 得出一个基因一个酶的假说。,Their work paved the way for other scientists to elucidate the precise ways in which enzymes affect complex metabolic pathways. 他们的工作为其他工作者铺平了道路，即精确地阐明了酶影响了复杂的新陈代谢途径。,In 1949, in research on the role of hemoglob
10、in(血红素)in sickle(镰刀) cell anemia(贫血症), Linus Pauling helped refine the one-gene-one-enzyme hypothesis into the one-gene-one-polypeptide hypothesis. 1949年，Linus Pauling对镰刀状细胞贫血症血红素的研究将一个基因一个酶的假说上升为一个基因一个多肽假说。,2. The search for the chemistry and molecular structure of nucleic acidsNuclei acids, origin
11、ally isolated by Johann Miescher in 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 年分离成功，二十世纪早期Feulgen用红色染料染色法证实核酸是染色体组最基本的成分。,Frederick Griffiths experiments with the Rough and
12、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对粗糙和光滑的肺炎双球菌实验表明，不确定的某种物质可以从一组细菌转移到另一种细菌中并能改变另一种细菌的物理属性。,In the 1940s the team of Avery, MacLeod, and McCarty showed that this unknown materia
13、l was DNA.二十世纪四十年代，Avery, MacLeod和McCarty研究小组确认该物质为DNA。,1935年，美国洛克菲勒学院的Osvald T. Avery和Colin M.MacLeod及Maclyn McCarty开始试图纯化能把R品系变成S品系的转化因子并鉴定其化学成分。1944年发表报告说，已将该物质分离出，活性极强。用蛋白酶或核酸酶处理不影响其转化能力，用DNA酶处理转化能力消失。,At about the same time P.A.Levene discovered that DNA contained four nitrogenous bases, each o
14、f which was attached to a sugar molecule and a phosphate group-a combination Levene termed a nucleotide几乎同时， P.A.Levene 发现DNA包含四种含氮碱基，每个碱基和磷酸分子分别连接在糖分子上，Levene把这个复合物称为核苷酸。,P.A.Levene (1869,2,25俄国Sasor-1940,9,6美国纽约)1891年毕业于圣彼得堡帝国军事医学院, 医学博士, 与其老师A.Kssel及同学W.Jones 一起弄清了弄清了核酸的基本化学结构,证实核酸是由许多核苷酸组成的大分子。核
15、苷酸是由碱基、核糖和磷酸构成。其中碱基有4种(腺瞟呤、鸟瞟呤、胞嘧啶和胸腺嘧啶),核糖有2种(核糖与脱氧核糖）,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.二十世纪五十年
16、代初期，关于DNA能否负载复杂的遗传信息的分歧结束， Martha Chase and Alfred Hershey,通过对大肠杆菌实验发现，遗传物质是DNA，而不是蛋白质。,Each DNA nucleotide contains a five-carbon sugar, deoxyribose, attached to one of four bases: adenine, guanine, cytosine, or thymine 每个核苷酸都含有一个五碳、脱氧核糖，分别连接4个碱基，即：腺嘌呤，鸟嘌呤，胞嘧啶，胸腺嘧啶。,Adenine and guanine molecules ar
17、e double-ring structures called purines, while cytosine and thymine are single-ring structures called pyrimidines.腺嘌呤和鸟嘌呤分子是双环结构叫嘌呤，胞嘧啶和胸腺嘧啶是单环结构叫嘧啶。,腺嘌呤,鸟嘌呤,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 s
18、ugar of one nucleoside to the five-carbon sugar of the next nucleoside in the chain. This phosphate bonding creates a sugar-phosphate backbone.碱基连接糖称核苷。磷酸键形成糖-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
19、 to that of guanine, and (2)the ratios of A to T and of C to G vary with different species. Chargaff定律说明（1）DNA中腺嘌呤与胸腺嘧啶，胞嘧啶与鸟嘌呤数量相等；（2）腺嘌呤与胸腺嘧啶，胞嘧啶与鸟嘌呤的比例随物种不同而不同。,3. The research race for the molecular structure of DNAIn the late 1940s and early 1950s, researchers looking for the structure of DNA d
20、rew upon Chargaffs insight, Levenes ideas on DNA components, and two other lines of evidence.40年代末50年代初，研究者在寻求DNA结构过程中，借鉴了Chargaff 的观点和Levene的组成理论以及其他两个线索。,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 diffrac
21、tion photos of DNA, showing a helical structure with distance between the coils, taken by Franklin and Wilkins.一个是Linus Pauling的假设，DNA可能具有螺旋的结构，通过氢键连接。另一个是DNA的X射线-衍射图片，图片显示卷曲间间隔呈螺旋结构，图片由Franklin and Wilkins提供。,Based on this information Watson and Crick proposed the double helix model of DNA-a twiste
22、d ladder -like molecule with two outer sugar phosphate chains and rungs(梯子的横档，梯级)formed by nucleotide pairs.基于这些信息，Watson 和 Crick提出了双螺旋结构模型，即DNA是一盘绕成梯子形状的分子，外部是两条糖磷酸链，核苷对形成梯子的横档。,Paired nucleotide, which always occur as A-T or G-C, are linked by hydrogen bonds. Watson and Crick also proposed that ge
23、netic information is encoded by the sequence of base pairs along the DNA molecule. A和T或者G和C配对，他们之间通过H键相连。Watson和Crick还提出遗传信息是由DNA分子的碱基对序列编码的。,4. How DNA replicatesIn their model of DNA structure and function, Watson and Crick hypothesized that DNA replicates itself by “unzipping” along the hydrogen
24、bonds joining A to T and C to G. Watson and Crick 假设DNA是以解开拉链方式自我复制的，即A和T以及C和G之间的氢键断裂。,This process would produce two opposite halves that could then serve as templates for the construction of new, complementary strands.这一过程将产生两条相反链，分别以其为模板生成新的、互补链。,This model of semiconservative replication-conserv
25、ative because each new molecule has one half of the former parent molecule-was later confirmed by the work of Meselson and Stahl. 此即为半保留复制，保留是因为每一新分子含有父母分子的一半，随后这一假设被Meselson 和 Stahl 所证实。,In E.coli DNA replication begins with the formation of a bubblelike structure on the circular chromosome that is
26、 produced by replication forks.大肠杆菌DNA复制开始时在环形染色体上形成泡状结构，那是由复制叉产生的。,Studies of bacterial DNA replication have shown 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).对细菌DNA复制的研究表明，链生长方向由5向3端，,The leading strand is synthesized
27、continuously ,while the lagging strand is synthesized in short stretches known as Okazaki fragments. 前导链连续生成，后随链由冈崎片段组成.,The enzyme DNA polymerase links free nucleotides as they line up(排成行)on the template formed by the original strand of the parent molecule.当核苷在亲本分子原始链形成的模板上排成行时，DNA聚合酶把这些自由的核苷连接到一起。,In eukaryotes DNA replication follows the same general principles as in prokaryotes . On the long DNA molecules replication proceeds(in two directions at once) from hundreds or thousands of points of origin.真核生物DNA复制与原核生物DNA复制相似，但有几百到几千个复制原点同时向两个方向进行。,在原核生物中，复制起始点通常为一个，而在真核生物中则为多个。,
