Content. 1. Introduction 2. The DNA is the material of inheritance 3. Replication 4. Repair 5. Genetic code 6. Mutation

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1 DNA

2 Content 1. Introduction 2. The DNA is the material of inheritance 3. Replication 4. Repair 5. Genetic code 6. Mutation

3 DNA determines who we are

4 DNA determines who we are

5 DNA and behavior DNA: our robotic self Brain: our free self.or?

6 The age of DNA Medicine and Biotechnology

7 1 The function of DNA 1. Transmission of genetic information (inheritance): - mediated by germ cells 2. Control of cell function: in each cell (in embryogenesis and adult body)

8 The DNA 2 ugust Weismann is the material of inheritance Localization: - In the nucleus - Weismann (1890): materials in the nucleus controls the cell function - In the chromosomes Chemical nature The big question: DNA or protein?

9 max Mutation efficiency max The DNA 3 is the material of inheritance Stadler and Über: The absorption spectrum of DNA and the effective spectrum of mutagenesis coincide (260 nm) - the maximal absorption of proteins is at 280 nm Mutagenezis Absorption spectrum (DNS) Absorption spectrum (protein) Wavelength (nm)

10 The DNA 4 Frederick Griffith is the material of inheritance Griffith: genetic transformation of nonvirulent pneumococci

11 The DNA 5 Oswald T. Avery is the material of inheritance Avery: genetic transformation by DNA

12 The DNA 6 Martha Chase Alfred Hershey is the material of inheritance The Herschey and Chase experiment Bacteriophage T2 attaches to the surface of a bacterium and injects its DNA. Viral genes take over the host s machinery and synthesizes new viruses. The bacterium bursts, releasing about 200 viruses.

13 The RNA 7 can also be the genetic material The Tobacco mosaic virus (TMV) experiment:

14 The structure of DNA 8

15 9 The structure of DNA Erwin Chargaff A = T; G = C Contradicts to Leven s tetranucleotide hypothesis (A=T=C=G) Chargaff s rule

16 10 The structure of DNA Alexander Todd Todd: phosphodiester bond nucleotides form polymers

17 10 The structure of DNA Alexander Todd Todd: phosphodiester bond nucleotides form polymers deoxyribose ribose 3 ester bond base 5 3 phosphate 5 deoxyribose

18 10 The structure of DNA Alexander Todd Todd: phosphodiester bond nucleotides form polymers Bases Sugar-phosphate backbone

19 11 The structure of DNA Rosalind Franklin Franklin: X-Ray crystallography helped reveal the structure of DNA

20 12 The structure of DNA James Watson Francis Crick DNA is a double helix Model building

21 12 The structure of DNA 3 end James Watson Francis Crick TA pairs have two hydrogen bonds. CG pairs have three hydrogen bonds. Base pairing in DNA is complementary 3 end 5 end

22 X H N N N N H H N H A O O H H N N H H H T O H N N N N H G N H H O H N N C N H H H deoxyribose deoxyribose deoxyribose deoxyribose The structure of DNA thymine (T) adenine (A) cytosine (C) guanine (G) 13

23 Characteristics of the genetic material and the DNA structure 14 James Watson Francis Crick (1) The genetic material stores an organism s genetic information - the combination of the bases can produce it (2) The genetic material is capable for mutation - changing of base pair sequences can produce it (3) The genetic material is precisely replicated - it is accomplished by the complementary base pairing (one DNA strand contains the information of the other strand

24 Nobel Prize in Physiology or Medicine (1962) 15 J.D.Watson F.H.Crick M.H.F. Wilkins What about R. Franklin?

25 16 DNA replication Arthur Kornberg Kornberg: in vitro DNA replication 3 subtances are needed : (1) DNA polymerase (isolated by Kornberg) (2) dntps: datp, dctp, dgtp, dttp (3) DNA template

26 17 DNA replication Matthew Meselson Frank Stahl The three possible models for DNA replication Semiconservative Conservative Dispersive

27 DNA replication 17 Meselson and Stahl s experiment: semiconservative DNA replication N 15 Heavy N N 14 Light N

28 DNA replication 18 The direction of new strand synthesis is 5 3

29 19 DNA replication RNA primer is needed for chain initiation

30 20 DNA replication Okazaki fragments leading strand parent strand leading strand lagging strand leading strand lagging strand

31 DNA replication 21

32 Repair 22

33 23 Genetic code The genetic code is composed of triplets Code: in DNA Codon: in mrna Anticodon: in trna Start codon: AUG Stop codons: UAA, UAG, UGA (1) The genetic code is composed of triplets: one triplet encode one amino acid (2) The genetic code is redundant: many amino acids are encoded by more than one triplets (3) The genetic code is comma-free : the triplets are not isolated units (4) The genetic code is universal: every living being is descended from a single common ancestor Few exception: mitochondria, chloroplasts, protistas - in 1-1 codons

34 24 Mutation alterations of the nucleotide sequence Somatic mutations occur in somatic (body) cells. Mutation is passed to daughter cells, but not to sexually produced offspring Germ line mutations occur in cells that produce gametes. Can be passed to next generation Point mutations: change in a single base pair loss, gain, or substitution of a base (can result from replication and proofreading errors, or from environmental mutagens) Chromosomal mutations: change in segments of DNA loss, duplication, or rearrangement Spontaneous mutations - occur with no outside influence. Several mechanisms: Induced mutation - due to an outside agent, a mutagen

35 25 Silent mutation - no change in amino acid sequence

36 26 Missense mutation - base substitution results in amino acid substitution

37 27 Missense mutation - Sickle allele for human β-globin is a missense mutation: glutamic acid valine at 6 th position - Individuals that are homozygous have sickle-cell disease

38 28 Nonsense mutation - base substitution results in a stop codon

39 29 Frame-shift mutation - single bases inserted or deleted usually leads to nonfunctional proteins

40 30 Chromosomal mutations Deletions Insertions Translocations

41 31 Mutation Mutation provides the raw material for evolution in the form of genetic diversity. Mutations can harm the organism, or be neutral. Occasionally, a mutation can improve an organism s adaptation to its environment, or become favorable as conditions change.

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