Lesson Five Discovering the Chemical Nature of the Gene
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.
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.
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).
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.
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.
Frederick Griffith and Oswald Avery separately conducted experiments in pneumococci ([7nju:mE5kCksai][微]肺炎双球菌), which led to the conclusion that DNA is the genetic material. • Using bacteriophages ([bAk5tiEriEfeidV]n.噬菌体), Alfred Hershey and Martha Chase confirmed that DNA, not protein, is the genetic material.
James Watson and Francis Crick subsequently established the double helical structure of DNA. Together, these scientists pioneered the field of molecular genetics.
glossary • Adenine[5AdEni:n] n.[生化]腺嘌呤 • Cytosine[5saitEsi:n]n.[生化]胞嘧啶 • Guanine[5^wB:ni:n]n.[生化]鸟嘌呤 • Thymine[5Waimi:n]n.[生化]胸腺嘧啶 • Uracil[5juErEsil] n.[生化]尿嘧啶 • Purine [5pjuEri:n]n.[生化]嘌呤 • Pyridine[9pai`rimidi:n]n.[化]嘧啶
Nucleoside [5nju:kliEsaid]n.[生化]核苷 • Cytidine[5saitEdin]n.[生化]胞苷 • Thymidine [5Waimi7di:n]n.[生化]胸(腺嘧啶脱氧核)苷 • Uridine[`jJErIdi:n]n.[生化]尿(嘧啶核)苷 • Adenosine[E`denEsi:n]n.[生化]腺苷 • Guanosine[5^wB:nEsin]n.[生化]鸟苷, • Ribonucleotide [7raibEu5nu:kliE7taid]n. 核(糖核)苷酸 • Deoxyribonucleotide[di:`Cksi9raibEJ`njU:kliEtBid] • [生化]脱氧核( 糖核)苷酸
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.
Structure of a DNApolymerase • -ase suff.（后缀）Enzyme:酶： • amylase.淀粉酶 Side view: Polymerase active site Top view with template-primer: Polymerase site And proofreading site
Section of a DNA molecule showing the double helix molecular shape Double helix 双螺旋
Semiconservative replication半保留复制 • Semi-pref.（前缀）表示“半,不完全地”之义 • Semicircle, semiconscious
helical 10 layer Lines Between Cross Patterns (10 Residues Per turn) X-ray diffraction X射线衍射 • Haemoglobin [7hi:mEu5^lEubin] • n.血色素, 血红蛋白 • myoglobin[7maiE5^lEubin] • n.肌球素, 肌红蛋白
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.
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
Hemoglobin 血红蛋白 • Linus Pauling • Defective hemoglobin molecules in Sickle-cell anemia (h) detected by electrophoresis[i9lektrEfE`ri:sis]n.电泳现象 • One-gene-one-polypeptide
正常红细胞与镰刀形红细胞的扫描电镜图 正常红细胞 镰刀形红细胞 -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…
2 The search for the Chemistry and Molecular Structure of Nucleic Acids Friedrich Miescher
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.
Oswald Avery (1877-1955) • 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.
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.
3 The Molecular Structure of DNA Evidence: 1. The suggestion of Linus Pauling 2. The X-ray diffraction
Linus Pauling (1901-1994) • 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.
Rosalind Franklin (1920-1958) • 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.
DNA The Code of LifeThe Molecular Basis of Inheritance • Deoxyribonucleic acid DNA • The 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.
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
The Discovery • The 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.
The Scientists • Francis 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.
Maurice Wilkins (1916- ) • 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.
Structure There are 4 different nucleotides in DNA Adenine pairs with Thymine Guanine pairs with Cytosine