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1868年,瑞士青年科学家 F.Miescher,从外科绷带上脓细胞的 细胞核中分离得到一种 含磷较高的酸性物质, 称之为核素(nuclein),核素实质是一种核糖核蛋白,核酸的发现,1889年,Altmann首先制备了不含蛋白的核酸制品,并引入“核酸”这一名词。 20世纪20年代测定了核酸的化学组成,并将核酸分为DNA和RNA。 1943年,E .Chargaff的工作:嘌呤:嘧啶=1:1,由此推理出碱基配对的理论。 1944年,Avery的肺炎双球菌转化实验,证明遗传物质即为DNA。 1953年,Watson-Crick建立了DNA的双螺旋结构模型。 之后,遗传密码的阐明、内切核酸酶的发现、核酸的合成与分析技术、基因重组技术等的建立形成了分子生物学的基本完整体系。,核酸的研究历史,核酸作为遗传物质的证明,三个经典实验 Frederick Griffith 和Oswald Avery的肺炎链球菌转化实验 Hershey & Chase的噬菌体感染实验 烟草花叶病毒()感染实验,Frederick Griffith In 1928 a scientist named Frederick Griffith was working on a project that enabled others to point out that DNA was the molecule of inheritance. Griffiths experiment involved mice and two types of pneumonia, a virulent and a non-virulent kind. He injected the virulent pneumonia into a mouse and the mouse died. Next he injected the non-virulent pneumonia into a mouse and the mouse continued to live. After this, he heated up the virulent disease to kill it and then injected it into a mouse. The mouse lived on. Last he injected non-virulent pneumonia and virulent pneumonia, that had been heated and killed, into a mouse. This mouse died. Why? Griffith thought that the killed virulent bacteria had passed on a characteristic to the non-virulent one to make it virulent. He thought that this characteristic was in the inheritance molecule. This passing on of the inheritance molecule was what he called transformation.,Griffith的实验,or,and,可分离,Oswald Avery Fourteen years later a scientist named Oswald Avery continued with Griffiths experiment to see what the inheritance molecule was. In this experiment he destroyed the lipids, ribonucleic acids, carbohydrates, and proteins of the virulent pneumonia. Transformation still occurred after this. Next he destroyed the deoxyribonucleic acid. Transformation did not occur. Avery had found the inheritance molecule, DNA!,Hershey & Chase (1952) - blender experiment bacteriophages are grown in radioactive medium proteins labeled with 35S DNA labeled with 32P during transformation of E. coli by bacteriophages, 32P goes in, 35S stays out = DNA is the transforming principle,T Bacteriophages (“Phage“) Bacteriophages are viruses that attack bacteria. They attach to the outside membrane of bacteria by means of the thin “tail“: the round “head“ contains DNA. The name means “bacteria eaters“ and is commonly shortened to just “phage“. Early biochemical and genetic studies of phage are the foundations of modern molecular biology.,The Hershey & Chase Experiment Growing bacteriophage (a virus that grows on bacteria) was differentially labelled with radioactive phosphorus (which labels nucleic acid) or radioative sulfur (which labels protein),The Hershey & Chase Experiment During the process of infection, a quick spin in a blendor shears phage away from the outside of the bacteria. Analysis of the bacterial and supernatant fractions afterward shows that phosphorus-labelled DNA inside the phage shows up in bacteria (left), whereas the sulfur-labelled protein in the external coat remains in the supernatant (right). Further, bacteria with labelled DNA go on to produce progeny phage that are also labelled. This biological experiment confirms Averys conclusion that DNA is the transforming substance, and shows that transformation is heritable.,Central Dogma,DNA可通过复制遗传给下一代,染色体是DNA的载体,(1)DNA是主要的生物遗传物质,人体23对染色体,分别来自于父母,,染色体上的DNA双螺旋,生物染色体有有丝分裂(无性繁殖)、减数分裂(有性繁殖) 高等动植物是一次有丝分裂和无数次减数分裂的结合.,实质上是DNA的复制和遗传表达。,DNA的组成差异决定了细胞中所有蛋白质、RNA的结构特征,子代利用遗传下来的DNA可以制造与父代相同的RNA、蛋白质,故龙生龙、凤生凤。,多细胞的DNA控制了细胞分化、个体形成乃至个体的生老病死。,提问:为什么DNA相同细胞形状各异、功能不同? 不同细胞不同部分DNA发挥了作用(即表达),其余DNA休眠。,任何一个多细胞生物的体细胞都含有完全相同的DNA。,Clone克隆,人工操作下的细胞无性繁殖过程。,当给予合适的条件时,任何一种体细胞都能变化为一个完整的个体体细胞克隆技术;,白 绵羊的体细胞核,黑 绵羊的去核卵细胞细胞质,植入,山羊子宫,?,多莉(1997.7.23),基因 (gene 开始、发育的意思) (古代)种质(猜想) (十九世纪)孟德尔遗传颗粒(推断) (二十世纪初)摩尔根染色体是基因的载体(蛋白质?核酸?) (1944年)DNA是基因的化学载体,基因(Gene)即DNA上能够编译一个蛋白质或RNA的最小单位,一个细胞内所有基因组合在一起统称为“基因组” 。 DNA 的所有功能本质上反映的是基因的功能。,基因3,假基因,基因间隔区,DNA双螺旋,98核中(染色体中) 真核 线粒体(mDNA) 核外 叶绿体(ctDNA) DNA 拟核 原核 核外:质粒(plasmid) 病毒:DNA病毒,一、核酸的种类和分布,核酸分为两大类: 脱氧核糖核酸 Deoxyribonucleic Acid (DNA) 核糖核酸 Ribonucleic Acid(RNA),核酸的种类、分布与功能,RNA主要存在于细胞质中,tRNA rRNA mRNA 其它:小分子细胞核RNA(snRNA)、染色质RNA(chRNA)、反义RNA(antisense RNA)、双链RNA(dsRNA)、细胞质小RNA(scRNA)、具有催化活性的RNA(ribozyme)、 病毒RNA:SARS,核酸的分布,1928年,英国科学家Griffith发现肺炎链球菌使小鼠死亡的原因是引起肺炎。细菌的毒性是由细胞表面中的多糖所决定的。,二、核酸的生物学功能 (一)DNA是主要的遗传物质,1944年,O.T.Avery(美) 肺炎链球菌的转化实验,首次 证明DNA是细菌遗传性状的转化 因子。,十年后证明DNA
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