1869 J. F. Miescher nuclein

1
???? ????

• ??? ??
• ??? ????????
• ??? ?????????
• ??? ?????
• ??? ???????

2
??? ??

• ???
• 1869 J. F. Miescher
  nuclein
• 1889 Altmann
  nucleic acid
• 1909 W. Johannsen gene
• 1910 T. H. Morgan
  role of the chromosome in heredity
• 1941 G. W. Beadle , E. L. Tetum one gene
  one enzyme
• 1944 O.Avery
  diplococcus pneumoniae transform
• 1953 J.Watson F.Crick DNA
  double helix
• 1966 R. W. Holley et al
  interpretation of the genetic code
• 1991 USA
  the Human Genome Project
• 1997 L. Wilmut et.al
  Dolly sheep
• 2001 USA, UK, France,
• Germany, Japan and China Human
  Genome Mapping
• 2002 Jun Yu et al Draft
  Sequence of the Rice Genome

3
James Watson (left) and Francis Crick
4
The Nobel Prize in Physiology or Medicine 1962
"for their discoveries concerning the molecular
structure of nucleic acids and its significance
for information transfer in living material"
Francis Harry Compton Crick James Dewey Watson Maurice Hugh Frederick Wilkins
     
Great Britain USA Great Britain
Institute of Molecular Biology Cambridge, Great Britain Harvard University Cambridge, MA, USA University of London London, Great Britain
1916 - 1928 - 1916 -
5
The Nobel Prize in Physiology or Medicine 1968
"for their interpretation of the genetic code and
its function in protein synthesis"
Robert W. Holley Har Gobind Khorana Marshall W. Nirenberg
        
USA USA USA
Cornell University Ithaca, NY, USA University of Wisconsin Madison, WI, USA National Institutes of Health Bethesda, MD, USA
1922 - 1993 1922 - 1927 -
6
???????Human Genome Project

• 1990?10????????????????HGP???
• 1998?5??????????????????????,?????3???,?2001?????
  ?????????,???HGP?????
• 1999?12?1???HGP????????,???????????22??????????
• 2000?3?14?????????????????????????,??????????????
  ,?????????????????????
• 2000?5???HGP??????????2003?6????2001?6??
• 2000?6?26?????????????????
• 2001?2???HGP(????????????)???????????????????????
  ??????????15????Nature?16??Science???

7
COVER Photograph of the Honghe Hani rice terraces
in Yunnan Province, China. In this issue, two
separate research groups report draft sequences
of two strains of rice--japonica and indica. In
addition, the Editorial, News Focus, Letters, and
Perspectives highlight the significance of the
rice genome to the world's population. Image
Liwen Ma and Baoxing Qiu, Beijing Genomics
Institute
??????,??????????????2002?4?5??????????
Science???14??????????????????????????(??)?????
?????,???????????????
8
??????? ??????(DNA)
???RNA ????(RNA) ??RNA
??RNA
9
????????? ??????(DNA)???????
???RNA ??????? ????(RNA)
??RNA?????
??RNA??????,
???????
10
??? ???????? ?????????
??(P)
??
??
???? (B-R-P)
??

??(R)
??
??(B-R)
??(B)
11
??
?? ????
12
??(base)
??? (adenine, A) ??? (guanine, G) ???
(cytosine, C) ????(thymine,T) ??? (uracil,U)

??(purine)
??(pyrimidine)
13
??
???(G) (2-??-6-???)
???(A) (6-????)
14
??
????(T) (5-?????)
???(U) (2,4-????)
???(C) (2-? 4-????)
15
?????????
16
??????? ??????

• 1.??
• ?? ?? ??
• ????????????N-9??????N-1???C-1???????

17
9
1
1?
1?
????? (??)
??????? (????)
18
2.???

• ??? ?? ??
• ????????
• ?????????(???C-2?? C-3??C-5???????C-3??C-5?
  )??????????????????????5?-???,?????C-5? ??????

19
?????? (???)
???????? (?????)
20
??? ?????????

• ???? ATP?
• ?????NAD? NADP ?FAD ?
• ???? ????( cyclic AMP, cAMP),????(cyclic GMP,
  cGMP)
• ???????PAPS?SAM?UDPG?UDPGA?CDP-??(???)?

21

? ? ?
AMP
ADP
ATP
22
5 ?
3 ?
3 ?,5 ?-cAMP
23
??? ?????

• ?????????????,?????????????????
• ???3?, 5? -?????,???????????????C-3??????????C-5?
  ????3? , 5???????
• ?????? 5???(?????), 3???(????)
• ?????? 5? ?3?,????????????

24
5'??? ????
G
???? (????)
A
3',5'? ????
A
T
3'??? ??
T
OH
25
G C A T T
5
3
OH
P
P
P
P
P
5 pGpCpApTpT-OH 3
5 G C A T T 3
G C A T T
26
?? DNA???

• 1.DNA?????
• ?dAMP?dGMP?dCMP?dTMP?????????3,5-???
  ???????????????????

27
2.DNA????? ?????

• ????
• (1)Chargaff ??(20??4050??)
• ?????DNA??????
• ???????????DNA???????
• AT,GC,AGTC
• (2)Wilkins ?Franklin?????X-???
• (3)Watson ?Crick???????(1953)

28
(No Transcript)
29
0.34nm
3.4nm
Major Groove
Minor groove
2nm
30
DNA??????????

• ?????????
• ???????????????,????(5 3?3 5)
• ????,A-T,G-C
• ????,???????
• ????2nm ??3.4nm ????10????,??????0.34 nm
• ??????????????????????????????(base-stacking
  force)

31
DNA?????????

• ?????(B-DNA)???????????
• A-DNA?????DNA??????????RNA????DNA-RNA???????????
  ??????????2.6nm???2.5nm,11???/?
• Z-DNA???CGCGCGCG????????????????????1.8nm???4.5n
  m?12??/????????Z?????

32
??
??
?
??
??
Z-DNA B-DNA
A-DNA
33
??DNA(triple helix DNA)
??H-DNA
34

• ?? ??DNA?????????????????????????
• ????Watson-Crick?????????,??????????????????????D
  NA???????(Hoogsteen base pairing)??????T-A-T
  ,C-G-C?
• ??????

35
3.DNA??????

• (?)????DNA?????
• ??????????????????,?????(supercoil)????????

36
(?)????DNA?????????????
37
(No Transcript)
38
(No Transcript)
39
Chromosome
chromatid
40
4.????DNA??????? (1)????????????
(2)???????(???????)
41
???????RNA??????
?? RNA??????

• ?????? ???
  ??
• ????RNA rRNA mt rRNA
  ???????
• ??RNA mRNA mt mRNA
  ???????
• ??RNA tRNA mt
  tRNA ?????
• ????RNA HnRNA
  mRNA???
• ??RNA SnRNA
  ??HnRNA??
• 
  ????
• ???RNA SnoRNA
  rRNA????
• 
  ??
• ???RNA scRNA/7SL-RNA
  ???????
• 
  ????????????

42
RNA secondary and tertiary structures. (a)
Stem-loops, hairpins, and other secondary
structures can form by base pairing between
distant complementary segments of an RNA
molecule. In stem-loops, the single-stranded loop
(dark red) between the base-paired helical stem
(light red) may be hundreds or even thousands of
nucleotides long, whereas in hairpins, the short
turn may contain as few as 6 8 nucleotides. (b)
Interactions between the flexible loops may
result in further folding to form tertiary
structures such as the pseudoknot. This tertiary
structure resembles a figure-eight knot, but the
free ends do not pass through the loops, so no
knot is actually formed.
43
1.tRNA??????

• ????
• ????DHU ?T???mG? mA?
• ????????DHU??????(?????) ?T???3??????
• ?L?????

44
9
1
1
5
1?
1?
1?
1?
?????? ?????? ??????? 7????? (
pseudouridine,? ) ( inosine, I ) (
dihydrouridine,DHU ) ( 7-methylguanosine,mG )
45

• ?????

46
3
OH
ACCA
CCA??
T??
C- G U- A C- G U G
5P
DHU?
C- G G-C
C
U
Am
DHU?
UA
C
G
D
A
A
C
D
f
T
Gm
Cm
G
D
D
D
A
A
A
D
G
G
A
T??
A
f
C
A
U
A
?????
G
A
U
?????
????
a.????????????
b.tRNA ??L?????
47
2.mRNA???
????mRNA
5 ???? ???
3 ??A?
5
3
AAAA An
m7Gppp

AUG GUG
UAA
5 ???? ??? 3 ????
48
5?
5?
(m6A.A.G.C.U)
(m6A.A.G.C.U)
mRNA?5?????m7GpppNm
49
3.rRNA???
????18S rRNA
???? 16S rRNA
50
31 proteins 23S RNA 5S RNA
50S
70S
21 proteins 16S RNA
30S
49 proteins 28S RNA 5.8S RNA
60S
80S
33 proteins 18S RNA
40S
51
(No Transcript)
52
??? ???????

• ?????????
• ??????,pI??
• ?????????
• 260nm??????
• ??????????????260nm?????( A260 )??
• ????????????260nm?????( A260 )???

53
?????????????

• 1.???????????????(??????????????),??????????????,
  ?????????????????????????
• 2.?????????,???????????????????????,?????????????
  ?????

54
The denaturation and renaturation of
double-stranded DNA molecules
55

• 3. ??????????????????,????????????????????????,??
  ?????????,?????????

??
??
56
??????????????,???????
??????????????????????,?????????
??
??
?
?
?
?
?
?
?
?
?
?
?
?
57
???? 1.????(15) 2.???(15)
3.???????(20) 4.?????????(20)
5.????????????(20) 6.?????(10)