Section 3:

Molecular Biology

Bilingual teaching as a reform

Is a stretch of dynamic biochemistry

Focus on the biosynthesis of 3 macromolecules:

DNA: replication

RNA: transcription

Protein: translation

Chapter 29 An Overview of Genetic InformationChapter 29 An Overview of Genetic Information

Which are macromolecules?

Life is produced by the metabolism of macromolecules

The function of life is executed by proteins, which encoded by nucleic acid

The second genetic codon

The second genetic codon……

生物进化的 C 值矛盾 (C value paradox of nucleotide)

The total amount of DNA in the genome of haploid

is a characteristic of each living species known as its

Maximum C value (单倍体基因组总 DNA 的含量 )

最大 C 值 (Maximum C value)

The total amount of DNA for encoding the genes

information is termed its Minimum c value （编码基

因信息的总 DNA含量）

最小 C 值 (Minimum c value)

C value paradox of nucleotide

霉菌藻类

G+细菌G-细菌

显花植物鸟类哺乳类爬行类两栖类硬骨鱼类软骨鱼类赖皮类甲壳类昆虫类软体动物蠕虫类

真菌

枝原体

A Is not linearly correlative with evolution extent

B The standard deviation varies in the same genus

C C value is far from c value.

（ Euk. 人体 c = C/10）

( Prok. Φx174 c ＞ C )

Eukaryote DNA chromosomes

（ 2C ）（ 2N）

两栖鲵 168.0 pg(10-12g) 24

肺鱼 100 38

蝾螈 85.3 24

警蛙 28.2 24

牛 6.4 60

人 6.4 46

绵羊 5.7 54

果蝇 0.2 8

贝母 196.7 24

豌豆 28 12

玉米 11 20

Prokaryote DNA

（ C）

Salmonella 0.0143 pg

E.coli 0.0040

T2 0.00022

λ 0.0000055

ΦΧ174 0.000005

Repeat sequence

单一序列长度愈小（重复度愈大） kinetic complexity(K.C.）愈小 Cot(1/2)值小（复性愈快）

poly(A ) K.C. = 1

Cot(1/2) = 2 × 10-6

T4 DNA K.C. = 1.7 × 106

Cot(1/2) = 0.3

E.coli DNA K.C. = 4.2×106 bp

Cot(1/2) = 9

DNA的复杂度：单倍体细胞基因组中非重复序列的碱基对数

DNA as a major genetic material

Experiment 1:

Marked protein by 35S

Marked DNA by 32P

Experiment 2:

35S can not enter the new cells.

However, 32P was found in the new cells.

German Fraenkel

Extract the RNA and protein of the virus individually.

Put them into the surface of the healthy leaves.

RNA caused the disease.

While protein can not.

Conclusion: Genetic material is RNA not protein.

Experiment 3:

Gregory Johann Mendel (1822-1884)

7 traits

phenotype

But where is the “genetic factor”?

Founder of modern genetics: Thomas Hunt Morgan

Tied genetic factor (gene) with chromosomes.

Sexual linkage by drosophila is regarded as the third discover in genetics because it brings together a specific gene and chromosomes.

If 2 genes are near in the same chromosome, maybe linked heredity.

If far, maybe exchanged-heredity.

Opportunity for exchange can be viewed as the distance of 2 genes

Essence of the genes

One gene, one enzyme

One peptide, one gene

Trait——protein——gene： Forward Biology

Gene——protein——trait ： Reverse Biology

DNA

Mostly in chromosome

Semi-autonomous organelle or

plasmid

Nucleus Cytoplast

Heredity

Category of genetic materials

In most cases DNA works as genetic material

RNA works in some viruses

Protein?

Functional diversity of RNA

Transferring and processing genetic information

Focused on protein synthesis

Messenger RNA

Transfer RNA

Ribosome RNA

RNA processing genetic information

General process

Recoding sequence

CutTrimmingAddingModificationIsomerization

Splicing

Editing

Recoding

Alternative transcript

1.Correcting tRNA and the second system of genetic codon

2.Sometimes tRNA will transfer an amino acid in nonsense mutations.

赭石突变（ UAA）琥珀突变（ UAG）乳白突变（ UGA ）

Recoding

nonsense mutations

RNA interfering干涉（干扰， RNAi）

The small double-strand RNA can inhibit gene expression.

C. Elegans or petunias (牵牛花 )？

More effective than Antisense RNA

Models

NatureDecipheringFeatureEffect of mutation

Universality

ORFs

Overlapping genes

Genetic codon

Nature

1. Genetic code is a triplet code

(three nucleotide encode one amino acid)

The way in which the nucleotide sequence in nucleic acids specifies the amino acid sequence in proteins.

The triplet codons are nonoverlapping and comma-less.

------UCU UCC CGU GGU GAAUCU UCC CGU GGU GAA------

2. Genetic code is degenerate :

Only 20 amino acids are encoded by 4 nucleotides in triplet codons (43 =64 of amino acids could potentially be encoded). Therefore, more than one triplet are used to specify a amino acids, and the genetic code is said to be degenerate, or to have redundancy.

Deciphering

System A: cell-free protein synthesizing system from E. coli

1. cell lysate treated by DNase to prevent new transcription

2. Add homopolymeric synthetic mRNAs [poly(A)] + 19 cold (non-labeled) and one labeled aminoacids

3. In vitro translation4. Analyze the translated polypeptides

poly(U) ---UUU--- polyphenylalanine

poly(C) ---CCC--- polyproline

poly(A) ---AAA--- polylysine

poly(G) --- did not work because of the complex secondary structure

Random co-polymers (e.g. U and G Random co-polymers (e.g. U and G in the same RNA) were used as in the same RNA) were used as mRNAs in the cell-free system to mRNAs in the cell-free system to determine the codon for many determine the codon for many amino acids.amino acids.

Features

Synonymous codons: 18 out of 20 amino acids have more than one codon

to specify them, causing the redundancy of the genetic code.

the third position:

pyrimidine ----synonymous (all cases)

purine ----synonymous (most cases)

the second position:

pyrimidine ----hydrophobic amino acids

purine -----polar amino acids

Effect of Mutation

1. Transition: the most common mutation in nature

changes from purine to purine, or pymidine to pymidine

At third position: no effect except for Met Ile; Trp stopsecond position: results in similar chemical

type of amino acids.

2. Transversions: purine pymidine At third position: over half have no

effect and result in a similar type of amino acid. (Example: Asp Glu)

At second position: change the type of amino acid.

In the first position, mutation (both transition and transvertion) specify a similar type of amino acid, and in a few cases it is the same amino acid.

Thus, natural triplet codons are Thus, natural triplet codons are arranged in a way to minimize arranged in a way to minimize the harmful effect of an the harmful effect of an mutation to an organism. mutation to an organism.

Summary

简并性 :64种密码子决定 20种氨基酸，重复，同义密码子

摆动性（变偶性）：反密码子的 3个碱基与密码子反向互补，前两个碱基严格互补，第三个可以摆动

普遍性：生物体普遍适用

偏爱性：不同生物体（线粒体）使用何种同义密码子有偏爱

Universality

• The standard codons are true for most organisms, but not for all.

Codon Usual meaning Alternative Organelle or organism

AGA AGG Arg Stop,Ser Some animal mitochondria

AUA Ile Met Mitochondria

CGG Arg Trp Plant mitochondria

CUN Leu Thr Yeast mitochondria

AUU GUG UUG

Ile Val Leu Start Some protozoans

UAA UAG Stop Glu Some protozoans

UGA Stop Trp Mitochondria,mycoplasma

ORFs

Open reading frames (ORFs) are suspected coding regions starting with ATG and end with TGA,TAA or TAG identified by computer.

When the ORF is known to encode a certain protein, it is usually referred as a coding region.

I coupled with U,A and C

Which codon can be recognized by Anticodon IGC？

Processing of RNA

Only the mature RNA could be translated.

The precursor of mRNA is called heterogeneous nuclear RNA, (hnRNA), which needs be processed.

Processing： Capping in 5 ， end

Poly A in 3 ， end

Cutting intron

Linked exon

m7G加在 5 ，端：

免受酶切

促进启始蛋白质合成