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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