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1、Nucleotides Deoxyribonucleic Acids (DNA) Ribonucleic Acids (RNA),Daochun Kong The College of Life Sciences Peking University,Deoxyribonucleic Acids (DNA),In 1868, Friedrich Miescher, a Swiss biologist, isolated a phosphorus-containing substance from the nuclei of pus cells (leukocytes), which he cal
2、led “nuclein”. He further found that the “nuclein” consisted of two portions. One portion is acidic, which we now know as DNA. The other portion is basic, which are mostly histone proteins. Thereofre, the “nuclein” Miescher isolated was actually chromatin. Later, he found that a similar substance in
3、 the heads of salmon sperm cells.,1. The Discovery:,2. DNA, the Genetic Substance:,1). DNA was suspected to be genetic material, but, there was more reason to assign this role to proteins. Proteins were thought to be larger, more complex (composed of twenty different amino acids), and therefore were
4、 more suitable for a genetic role. DNA was thought to be just a repeating polymer of one kind of tetranucleotide unit. It was just about seventy years ago, in1930s, DNA was widely believed to exist only in animal cells, and RNA was in plant cells. Plant and animal cells were sometimes distinguished
5、based on this chemical feature.,2). In 1928, Frederick Griffith discovered the phenomenon of transformation in bacteria,Streptococcus pneumoniae has two forms, Slimy colonies (virulent S strain) forms mucous capsules, it kills mice. But, heat-killed strain does not kill mice. Rough colonies (non-vir
6、ulent R strain) lacks capsules, it does not kill mice. Mixed heat-killed S-strain with live R-strain, resulting organisms killed mice. Conclusion: some chemical in cells of S strain is stable in heat treatment, retains genetic information, is able to transmit that information to R-strain bacteria, c
7、onvert them to S.,3). In 1944, Avery, MacLeod, and McCarty found that DNA prepared from a virulent strain of pneumococcus could transform a nonvirulent strain of this organism into a virulent one.,Virulent bacteria,Injection,Mouse dies,Nonvirulent bacteria,Mouse lives,Avery OT, MacLeod CM, McCarty M
8、 (1944) J. Exp. Med. 79:137.,Nonvirulent bacteria,DNA from virulent bacteria,DNA carried a genetic message from one type of cells could be assimilated and expressed by another type of cells.,Conclusion:,Argument: At that time, not everyone accepted Avery et als conclusion. The critics attacked that,
9、 a. The DNA was possibly contaminated by slight amount of proteins that was responsible for the observed transformation. b. DNA may be genetic substance just in bacteria.,What are your experiments to ease or eliminate these critics doubts?,4). In 1952, Alfred D. Hershey and Martha Chase discovered t
10、hat it was bacteriophage T2 DNA that entered host cell, E. coli, and carried genetic information for phage replication.,At that time, it was already known, a. Bacteriophage contains only DNA and proteins. b. Phage proteins do not have phosphorus P, but do contain sulfur S in amino acids. DNA does no
11、t have S, but lots of P.,Hershey and Chases experiment,5). In 1953, Watson and Crick, based on experimental evidences provided by the other people, suggested a model for structure of DNA - a complementary, double stranded, and helical structure of DNA. This model was proved correct several years lat
12、er.,Based on the above and other studies, it is finally demonstrated that DNA is indeed genetic substance. It has two discrete functions - One is to carry genetic information that brings about the specific phenotype of the cell; Another is its own replication.,How many kinds of nucleic acids? Chemic
13、al constituents of nucleic acids 3. Structure of nucleic acids? 4. Chemical properties of nucleic acids?,3. Chemistry of Nucleic Acids,Two Kinds of Nucleic Acids in All Organisms,DNA - Deoxyribonucleic acids RNA - Ribonucleic acids,1. DNA is a long linear polymer composed of four kinds of monomer un
14、its called deoxyribonucleotides (A, G, T, C) linked to each other in a chain.,DNA,5-AGTCCCTAGGACTATTTAAAACCTGGAGAGT- 3,2. Single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). In nature, most of DNA is in the form of dsDNA.,RNA,RNA is also linear polymers composed of four types of ribonucleot
15、ides (A, G, C, U). 5AGCUAAGUCCUUUGGGAACCCAAGGUUAACC3 Ribosomal RNAs (rRNA) Messenger RNAs (mRNAs) Transfer RNAs (tRNAs) and Other RNA molecules,Chemical Structure of Nucleotides,Alexander R. Todd (1954) chemical structure of the nucleic acids. PNAS. 40: 748-755,Differences of Nucleotides between DNA
16、 and RNA,Deoxyadenylate Deoxyguanylate Deoxythymidylate Deoxycytidylate Deoxyribonucleotides,Adenylate Guanylate Uridylate Cytidylate Ribonucleotides,Some Rare Bases in DNA and RNA,5-Methylcytidine N6-Methyladenosine,N2-Methyladenosine,5-Hydromethylcytidine,Inosine Pseudouridine,7-Methylguanosine 4-Thiouridine,Rare bases in DNA Rare bases in RNA,DNA,RNA,DNA & RNA Polymer,Individual nucleosides are joined toge
