第一节 遗传的分子基础(2)Molecular Basis of Inheritance

五、基因的表达与调控 (Gene expression and Regulation)六、基因突变与修复 (Gene mutation and Repair)

四、 DNA 复制 (DNA Replication)

四、 DNA 复制（ 1 ）DNA Replication

General features of Eukaryotic DNA Replication

四、 DNA 复制（ 2 ）

1. Semiconservative Replication ( 半保留复制 )

2. Semidiscontinuous Replication ( 半不连续复制 )

DNA Replication

Replication results in two daughter DNA moleculars, each consisting of one old strand from parental DNA molecular and one new strand

Parental DNA molecular

Second-generation

四、 DNA 复制（ 3 ）DNA Replication - Semiconservative Replication

First-generation

DNA replication ensures that all the somatic cells in a multicellular organism carry the same genetic information. It is also mean by which genetic instructions are copied for the next generation of the organism.

DNA Replication - Semiconservative Replication

四、 DNA 复制（ 4 ）

Biological function:

RNA 引物冈崎片段

前导链

后随链复制叉

The two strands of the original (parental) DNA molecular serve as templates for making new (daughter) strands. DNA replication begins at sites called origins of replication and proceeds in both directions.

Semidiscontinuous Replication

DNA Replication - Semiconservative Replication

四、 DNA 复制（ 5 ）

Both strands are replicated in the 5’→3’ direcion.

leading strand: One strand is replicated continuously in the direction of the movement of the replicating fork 。

Lagging strand: The other is replicated discontinuously as 1-2 kb Okazaki fragments in the opposite direction.

四、 DNA 复制（ 6 ）DNA Replication - Semiconservative Replication

Replicon ( 复制子 )

The DNA under the control of one origin of replication is called a replocon, even thought it may require two replicating forks.

Human genome: about 10000 replicons.

Replication of eukaryotic DNA is bidirectional.

DNA Replication

四、 DNA 复制（ 7 ）

第一节 遗传的分子基础（ 2 ）——

Molecular Basis of Inheritance

gene expression and regulation (transcription and translation)

五、基因的表达与调控（转录和翻译）

transcription-----DNA RNA

replication--- DNA DNA

Difference between transcription and replication

五、基因的表达与调控（ 1 ）gene expression and regulation

五、基因的表达与调控（ 2 ）gene expression and regulation - transcription

                                            

           

五、基因的表达与调控（ 3 ）gene expression and regulation - transcription

Coding strand: the DNA strand which has the same base sequence as the RNA transcript produced (although with thymine replaced by uracil).

Non-coding strand: The DNA strand that forms the template for both the transcribed mRNA and the coding DNA strand. (antisense strand, template strand).

五、基因的表达与调控（ 4 ）gene expression and regulation - transcription

Coding strand

Non-coding strand

五、基因的表达与调控（ 5 ）

⑴ Splicing （剪接） ⑵ Capping （戴帽） ⑶ Tailing （加尾）

核内异质 RNA (hnRNA): mRNA 前体 (mRNA precursor) 。

Maturesized mRNA

Post-transcriptional modification

Post-transcriptional modification

gene expression and regulation - transcription

五、基因的表达与调控（ 6 ）

⑴ Splicing （剪接）

gene expression and regulation - transcription

5′— 5′

五、基因的表达与调控（ 7 ）

⑵ Capping （戴帽）

gene expression and regulation - transcription

五、基因的表达与调控（ 8 ）

⑶ Tailing （加尾）

gene expression and regulation - transcription

五、基因的表达与调控（ 9 ）gene expression and regulation - transcription

Transcription start sites

RNA processing

mRNA

Transcription stop sites

三联体密码（ triplet code)

或密码子（ codon ）

五、基因的表达与调控（ 10 ）gene expression and regulation -translation

Translation is the process by which ribosomes read the genetic message in mRNA and produce a protein product according to the message’s instructions

密码表 (The dictionary of the genetic code)

五、基因的表达与调控（ 11 ）gene expression and regulation -translation

五、基因的表达与调控（ 12 ）gene expression and regulation - transcription

Degenerate( 简并性 ) ： More than one triplet codes for a given amino acid.

Universal ( 通用性 ): Almost organisms, from bacteria to human, are shown to share the same code.

AUG ： Met ( 蛋氨酸 , 甲硫氨酸 ) ； start code.

UAA 、 UAG 、 UGA ： stop code.

五、基因的表达与调控（ 13 ）

Reverse

transcription

Central dogma中心法则

原核生物基因表达调控系统——

E.coli 乳糖操纵子 (E.coli Lactose Operon)

五、基因的表达与调控（ 14 ）gene expression and regulation

五、基因的表达与调控（ 15 ）gene expression and regulation

By grouping functionally related genes together so they can be regulated together easily. Such a group of contiguous, controlled genes is called an operon.

Structural gene

Operator

Promoter

Regulatory gene (regulator)

乳糖操纵子 Lactose operonOperon:

五、基因的表达与调控（ 16 ）gene expression and regulation

Operon: repression

五、基因的表达与调控（ 17 ）gene expression and regulation

Induction: lactose

五、基因的表达与调控（ 18 ）gene expression and regulation

五、基因的表达与调控（ 19）gene expression and regulation

Regulation of gene expression:

complexity

multilevel regulation

五、基因的表达与调控（ 20 ）gene expression and regulation

1 Pre-transcription: the change of chromatin structure.

2 Transcription

3 Post-transcription: The RNA processing.

4 Translation

5 Post-translation: the modification of protein.

突变（ mutation ） : Any change in the nucleotide sequence of DNA (heritable differences in DNA sequence).

mutation

染色体畸变（ chromosome aberration ）： Any change in number or structure of chromosome基因突变（ gene mutation ）： any change in the nucleotide sequence of DNA.

一、 The type of mutation

1.Different stage of development

Somatic cell mutation

Reproductive cell mutation

六、基因突变和修复（ 1 ）Mutation and repair

2.Mutation factor Induced mutation （诱发突变）

Spontaneous mutation （自发突变）

3.Mutation result

Forward mutation （正向突变） Suppressor mutation （负向突变）

4.Change in DNA sequence

Sequence change (多点突变 ):

Point mutation (点突变 ) ：transition

transvertion

deletion

insertion

Mutation and repair

六、基因突变和修复（ 2 ）

六、基因突变和修复（ 3 ）

Biological response to DNA mutation (1)

Mutation and repair

Hereditary disorder

镰刀形红细胞贫血症 Sickle-cell disease

六、基因突变和修复（ 4 ）

Biological response to DNA mutation (2)

Mutation and repair

Benefits:

1 genetic diversity → evolution

2 survival advantage

六、基因突变和修复（ 5 ）

Biological response to DNA mutation (2)

Mutation and repair

二、基因突变的种类（一） Point mutation (碱基替换）

Transition ( 转换 )

Transversion ( 颠换 )

purine→purine， pyrimidine→pyrimidine

purine→pyrimidine, pyrimidine →purine

T

G

C

A

六、基因突变和修复（ 5 ）Mutation and repair

基因突变的效应 (the response of gene mutaion):

1 、 Same-sense or synonymous mutation （同义突变） CCA→ 脯氨酸，当 A→G 后， CCG→ 脯氨酸。 2 、 Missense mutation （错义突变 ): GAG→ 谷氨酸， A→T ， GUG→ 缬氨酸。

3 、 Non-sense mutation （无义突变 ) ： TAC→ 酪氨酸， C → A ， UAA→ 终止信号。

六、基因突变和修复（ 7 ）Mutation and repair

4 、 termination codon mutation, elongtion mutation

( 终止密码突变 , 也称延长突变） .

六、基因突变和修复（ 8 ）Mutation and repair

TAA → TAC

（二） frame-shift mutation ( 移码突变）

六、基因突变和修复（ 9 ）Mutation and repair

A A A C C C T T T G G G C A T G T G CC G

T T T G G G A A A C C C G T A C A C GG C

A A A C C C T T T G G G C A T G T G CC G

T T T G G G A A A C C C G T A C A C GG C

C

G

A A A C C T T T G G G C A T G T G CC G

T T T G G A A A C C C G T A C A C GG C

（三） codon mutation ( 整码突变）， codon insertion or

deletion ( 又称为或密码子插入或丢失）

六、基因突变和修复（ 10 ）Mutation and repair

A A A C C C T T T G G G C A T G T G CC G

T T T G G G A A A C C C G T A C A C GG C

A A A C C C T T T G G G C A T G T G CC G

T T T G G G A A A C C C G T A C A C GG C

C

G

C C

G G

A A A T T T G G G C A T G T G CC G

T T T A A A C C C G T A C A C GG C

A A A T T T G G G C A T G T G CC G

T T T A A A C C C G T A C A C GG C

A A A C C C T T T G G G C A T G T G CC G

T T T G G G A A A C C C G T A C A C GG C

C

G

A A A C C T T T G G G C A T G T G CC G

T T T G G A A A C C C G T A C A C GG C

C

G

C C

G G

A A A T T T G G G C A T G T G CC G

T T T A A A C C C G T A C A C GG C

A A A T T T G G G C A T G T G CC G

T T T A A A C C C G T A C A C GG C

Frame shift mutation

六、基因突变和修复（ 11 ）Mutation and repair

Codon mutation

（四） Dynamic mutation (Dynamic mutation ( 动态突变 ))

六、基因突变和修复（ 12 ）Mutation and repair

It is an unstable heritable element where the probability of mutation is a function of the number of copies of the mutation. That is, the replication product of a dynamic mutation has a different likelihood of mutation than its predecessor. These mutations, typically short sequences repeated many times, give rise to numerous known diseases including the Trinucleotide repeat disorders

The repair of DNA damage

1. Enzymatic Photoreactivation of Base Damage (光修复 )

Photoreactivating enzyme( 光复活酶 )

六、基因突变和修复（ 13 ）Mutation and repair

nick nick

六、基因突变和修复（ 14）Mutation and repair

2 ． Nucleotide Excision Repair (NER) ( 核苷酸切除修复 )

六、基因突变和修复（ 15 ）Mutation and repair

2 ． Nucleotide Excision Repair (NER)( 核苷酸切除修复 )

Lindahl T. et al. Science, 1999.

3 、 repair of post-replication ( 复制后修复 )

replication

recombination

re-synthesis

六、基因突变和修复（ 16）Mutation and repair