DNA

Content

1. Introduction

2. The DNA is the material of inheritance

3. Replication

4.Repair

5.Genetic code

6. Mutation

DNA determines who we are

DNA determines who we are

DNA and behavior

DNA: our robotic self

Brain: our free self

….or?

The age of DNAMedicine and Biotechnology

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)

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The DNA is the material of inheritanceAugust Weismann

Localization:

The big question: DNA or protein?

Chemical nature

- In the nucleus- Weismann (1890): materials in the nucleus controls the cell function

- In the chromosomes

2

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

The DNA is the material of inheritance

Wavelength (nm)

Mu

tati

on

eff

icie

ncy

Absorption spectrum (DNS)

Absorption spectrum (protein)

ma

x

ma

x

Mutagenezis

3

The DNA is the material of inheritance

Griffith: genetic transformation of nonvirulent pneumococci

Frederick Griffith

4

The DNA is the material of inheritance

Avery: genetic transformation by DNA

Oswald T. Avery

5

The DNA is the material of inheritance

The Herschey and Chase experiment

Martha Chase Alfred Hershey

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.

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The Tobacco mosaic virus (TMV) experiment:

The RNA can also be the genetic material

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The structure of DNA8

Chargaff’s rule

A = T; G = C Contradicts to Leven’s tetranucleotide hypothesis (A=T=C=G)

Erwin Chargaff

The structure of DNA9

Alexander Todd

Todd: phosphodiester bond – nucleotides form polymers

The structure of DNA10

Alexander Todd

deoxyribose ribose

ester bond

phosphate

deoxyribose

base

5’

5’

3’

3’

Todd: phosphodiester bond – nucleotides form polymers

The structure of DNA10

Alexander Todd

Todd: phosphodiester bond – nucleotides form polymers

The structure of DNA

Sugar-phosphate backbone

Bases

10

The structure of DNARosalind Franklin

Franklin: X-Ray crystallography helped reveal the structure of DNA

11

The structure of DNAJames Watson Francis Crick

DNA is a double helix

Model building

12

Base pairing in DNA is complementary

5′ end

3′ end

TA pairs have two

hydrogen bonds.

CG pairs have three

hydrogen bonds.

3′ end

The structure of DNAJames Watson Francis Crick

12

X

H

N

N

NN

H

H

NH

A

O

O

H

HN

N

H

H

H

T

O

H

N

N

NN

H

G

NH H

O

HN

N

C

N

H H

H

deoxyribose

deoxyribose

deoxyribose

deoxyribose

The structure of DNA

thymine (T) adenine (A) cytosine (C) guanine (G)

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James Watson Francis Crick

Characteristics of the genetic material

and the DNA structure

(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

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Nobel Prize in Physiology or Medicine (1962)

J.D.Watson F.H.Crick M.H.F. Wilkins

What about R. Franklin?

15

Kornberg: in vitro DNA replication

Arthur Kornberg

3 subtances are needed :

(1) DNA polymerase (isolated by Kornberg)

(2) dNTPs: dATP, dCTP, dGTP, dTTP

(3) DNA template

DNA replication

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DNA replication

The three possible models for DNA replication

Conservative

Semiconservative

Dispersive

Matthew Meselson Frank Stahl

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DNA replicationMeselson and Stahl’s experiment: semiconservative DNA replication

N15

N14

Heavy N

Light N

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DNA replicationThe direction of new strand synthesis is 5’ 3’

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DNA replication

RNA primer is needed for chain initiation

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DNA replication

lagging strand

leading strand

leading strand

parent strand

leading strand

lagging strand

Okazaki fragments

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DNA replication21

Repair22

Genetic code

(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

The genetic code is composed of triplets

Start codon: AUG

Stop codons: UAA, UAG, UGA

Code: in DNA

Codon: in mRNA

Anticodon: in tRNA

--------

Few exception: mitochondria, chloroplasts, protistas - in 1-1 codons

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Mutation

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

alterations of the nucleotide sequence

----------

----------

Spontaneous mutations

- occur with no outside influence. Several mechanisms:

Induced mutation

- due to an outside agent, a mutagen

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Silent mutation- no change in amino acid sequence

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- base substitution results in amino acid substitution

Missense mutation26

- Sickle allele for human β-globin is a missense mutation: glutamic acid valine at 6th position

- Individuals that are homozygous have sickle-cell disease

Missense mutation27

- base substitution results in a stop codon

Nonsense mutation28

- single bases inserted or deleted—usually leads to nonfunctional proteins

Frame-shift mutation29

Deletions

Chromosomal mutations

Translocations

Insertions

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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.

Mutation

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