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Lesson Five

Discovering the Chemical Nature of the Gene

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What are genes?

Genes are hereditary units that occupy specific locations on chromosomes and determine particular characteristics in an organism.

Genes exist in a number of different forms and can undergo mutation.

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Genes are working subunits of DNA. DNA is a

vast chemical information database that carries

the complete set of instructions for making all the

proteins a cell will ever need. Each gene contains

a particular set of instructions, usually coding for

a particular protein.

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Nucleic acids are often considered as the most

important macromolecules in cells. They store

genetic information and determine the primary

structure of proteins. There are two kinds of

nucleic acids: deoxyribonucleic acid (DNA)

and ribonucleic acid (RNA).

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DNA exists as two long, paired strands spiraled into the

famous double helix. Each strand is made up of millions

of chemical building blocks called bases. While there are

only four different chemical bases in DNA (adenine,

thymine, cytosine, and guanine), the order in which the

bases occur determines the information available, much as

specific letters of the alphabet combine to form words and

sentences.

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In the early 1900s, although scientists recognized that chromosomes are composed of DNA and proteins, few thought that DNA is the genetic material. Instead, the case for protein being the genetic material was very strong.

This view started to change in the later 1920s, when experiments with microorganisms yielded some surprising results.

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Frederick Griffith and Oswald Avery separately conducted experiments in pneumococci ([][ 微 ] 肺炎双球菌 ), which led to the conclusion that DNA is the genetic material. Using bacteriophages ([]n. 噬 菌体 ), Alfred Hershey and Martha Chase confirmed that DNA, not protein, is the genetic material.

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James Watson and Francis Crick subsequently established the double helical structure of DNA. Together, these scientists pioneered the field of molecular genetics.

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glossary Adenine[] n.[ 生化 ] 腺嘌呤 Cytosine[]n.[ 生化 ] 胞嘧啶 Guanine[]n.[ 生化 ] 鸟嘌呤 Thymine[]n.[ 生化 ] 胸腺嘧啶 Uracil[] n.[ 生化 ] 尿嘧啶 Purine []n.[ 生化 ] 嘌呤 Pyridine[]n.[ 化 ] 嘧啶

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Nucleoside [].[ 生化 ] 核苷 Cytidine[]n.[ 生化 ] 胞苷 Thymidine []n.[ 生化 ] 胸 ( 腺嘧啶脱氧核 ) 苷 Uridine[]n.[ 生化 ] 尿 ( 嘧啶核 ) 苷 Adenosine[]n.[ 生化 ] 腺苷 Guanosine[]n.[ 生化 ] 鸟苷 ,

Ribonucleotide []n. 核 ( 糖核 ) 苷酸 Deoxyribonucleotide [] [ 生化 ] 脱氧核 ( 糖核 ) 苷酸

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Nucleic acids consist of covalently linked monomers

called nucleotides.

Each nucleotide has 3 parts: a pentose (deoxyribose for

DNA and ribose for RNA), a nitrogenous base, and a

phosphate group.

There are two kinds of nitrogenous bases: pyrimidines and

purines. Purines have a six-atom ring fused to a five-atom

ring, while pyrimidines have only a six-atom ring.

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Side view:Polymerase active site

Top view withtemplate-primer:Polymerase siteAndproofreading site

Structure of a DNA polymerase

-ase suff. （后缀） Enzyme: 酶： amylase. 淀粉酶

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Section of a DNA molecule showing the double helix molecular shape

Double helix 双螺旋

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Okazaki fragment 冈崎片段[]

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Replication fork 复制叉

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Semiconservative replication 半保留复制

Semi-pref. （前缀）表示“半 , 不完全地”之义

Semicircle, semiconscious

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X-ray diffraction X 射线衍射

Haemoglobin [] n. 血色素 , 血红蛋白 myoglobin[] n. 肌球素 , 肌红蛋白

helical

10 layer Lines BetweenCrossPatterns(10 ResiduesPer turn)

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Text 1 Genes Code for Particular Proteins How was the fundamental relationship between

genes and proteins discovered? In 1909, British physician Archibald Garrod first

suggested that genes dictate phenotypes through enzymes that catalyze specific chemical reactions.

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Beadle and Tatum exposed bread mold to X-rays, creating mutants that were unable to survive on minimal medium as a result of inability to synthesize certain molecules

Using crosses, they identified three classes of arginine-deficient mutants, each lacking a different enzyme necessary for synthesizing arginine

They developed a “one-gene-one-enzyme” hypothesis, which states that each gene dictates production of a specific enzyme

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Hemoglobin 血红蛋白

Linus Pauling Defective hemoglobin molecules in Sickle-cell anemia

(h) detected by electrophoresis[]n. 电泳现象

One-gene-one-polypeptide

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正常红细胞与镰刀形红细胞的扫描电镜图

- 链 N 端氨基酸排列顺序 1 2 3 4 5 6 7 8

Hb-A （正常人） Val-His-Leu-Thr-Pro-Glu-Glu-Lys…

Hb-S （患 者） Val-His-Leu-Thr-Pro-Val-Glu-Lys…

镰刀形红细胞

正常红细胞

22Friedrich Miescher

2 The search for the Chemistry and Molecular Structure of Nucleic Acids

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Frederick Griffith: transforming principle

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History Search for genetic material:1952 - Hershey-Chase Experiment

Side by side experiments are performed with separate bacteriophage (virus) cultures in which either the protein capsule is labeled with radioactive sulfur or the DNA core is labeled with radioactive phosphorus.The radioactively labeled phages are allowed to infect bacteria. Agitation in a blender dislodges phage particles from bacterial cells. Centrifugation concentrates cells, separating them from the phage particles left in the supernatant. Results:Radioactive sulfur is found predominantly in the supernatant. Radioactive phosphorus is found predominantly in the cell fraction, from which a new generation of infective phage can be isolated. Conclusion: The active component of the bacteriophage that transmits the infective characteristic is the DNA. There is a clear correlation between DNA and genetic information.

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1944 by Osward T. Avery

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Microbiologist Avery led the team that showed that DNA is the unit of Inheritance. One Nobel laureate has called the discovery "the historical platform of modern DNA research", and his work inspired Watson and Crick to seek DNA's structure.

Oswald Avery (1877-1955)

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Chargaff and Chargaff’s rules

Erwin Chargaff (1905-2002) Chargaff discovered the pairing rules of DNA

letters, noticing that A Matches to T and C to G.

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3 The Molecular Structure of DNA

Evidence:

1. The suggestion of Linus Pauling

2. The X-ray diffraction

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The titan of twentieth-century chemistry.

Pauling led the way in working out the

structure of big biological molecules, and

Watson and Crick saw him as their main

competitor. In early 1953, working

without the benefit of X-ray pictures, he

published a paper suggesting that DNA

was a triple helix.

Linus Pauling (1901-1994)

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Franklin, trained as a chemist, was

expert in deducing the structure of

molecules by firing X-rays through

them. Her images of DNA - disclosed

without her knowledge - put Watson and

Crick on the track towards the right

structure. She went on to do pioneering

work on the structures of viruses.

Rosalind Franklin (1920-1958)

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Crystalline DNA

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Watson and CrickThe foundation of molecular biology

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4 how DNA replicates

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DNA The Code of Life The Molecular Basis of Inheritance

Deoxyribonucleic acid DNAThe information necessary to sustain and perpetuate life is found within a molecule. This is the genetic material that is passed from one generation to the next---a blue print for building living organisms.

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History Classic experiments for evidence

Griffith: transformation

Hershey-Chase: DNA necessary to

produce more virus

Other supporting evidence

DNA volume doubles before cells divide

Chargaff: ratio of nucleotides A = T and

G = C

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The DiscoveryThe DNA molecule was discovered in 1951 by

Francis Crick, James Watson and Maurice

Wilkins using X-ray Diffraction. In Spring 1953,

Francis Crick and James Watson, two scientists

working at the Cavendish Laboratory in

Cambridge, discovered the structure of the DNA

a double helix, or inter-locking pair of spirals,

joined by pairs of molecules.

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Watson and Crick with their

DNA model

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The ScientistsThe ScientistsFrancis Crick was born in 1916. He went to London

University and trained as a physicist. After the war he

changed the direction of his research to molecular

biology.

James Watson was an American, born in 1928, so aged

only 24 when the discovery was made. He went to

Chicago University aged only 15 and had already

worked on DNA.

Crick, Watson and Wilkins won the Nobel Prize for

medicine in 1962.

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Like Crick, New Zealand-born Wilkins

trained as a physicist, and was involved

with the Manhattan project to build the

nuclear bomb. Wilkins worked on X-ray

crystallography of DNA with Franklin at

King's College London, although their

relationship was strained. He helped to

verify Watson and Crick's model, and

shared the 1962 Nobel with them.

Maurice Wilkins (1916- )

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Structure

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There are 4 different nucleotides in DNA

AdenineAdenine pairs with ThymineThymineGuanineGuanine pairs with CytosineCytosine

Structure