Download ucla1 - WEHI Bioinformatics

Blueprint of Life
Based on Chapter 1 of
Post-genome Informatics
by Minoru Kanehisa,
Oxford University Press, 2000
Genome and gene
Entity
Genome
Definition
Unit of information transmission
Molecular Mechanisms
DNA replication
Gene
Unit of information expression
Transcription to RNA
Translation to protein
Nucleic acid and proteins
Macromolecule
Nucleic
acid
Protein
Backbone
Repeating unit
Length
Role
DNA
Phosphodiester bonds Deoxyribonu cleotides 103-10 8
(A, C, G, T)
RNA
Phosphodiester bonds Ribonucleo tides
(A, C, G, U)
103-10 5
103-10 4
102-10 3
Genome
Messenger
Gene product
Peptide bonds
102-10 3
Gene product
Amino acids
(A, C, D, E, F, G, H,
I, K, L, M, N, P, Q,
R, S, T, V, W, Y)
Genome
Nucleotide codes
A
Adenine
W
Weak (A or T)
G
Guanine
S
Strong (G or C)
C
Cytosine
M
Amino (A or C)
T
Thymine
K
Keto (G or T)
U
Uracil
B
Not A (G or C or T)
R
Purine ( A or G)
H
Not G (A or C or T)
Y
Pyrimidin e (C or T)
D
Not C (A or G or T)
N
Any nucleotide
V
Not T (A or G or C)
BASES
Adenine
Thymine
Guanine
Cytosine
Uracil
The Four Nucleosides of DNA
A nucleoside is a sugar, here deoxyribose, plus a base
dA = deoxyadenosine, etc.
dA
dG
PURINES
dC
dT
PYRIMIDINES
Base Pairing
The monomeric units
of nucleic acids are
called nucleotides.
A nucleotide is a phospate,
a sugar, and a purine or a
pyramidine base.
DNA:
B form
(7BNA)
Amino acid codes
Ala
Arg
Asn
Asp
Cys
Gln
Glu
Gly
His
Ile
Leu
Lys
Met
Phe
Pro
Ser
Thr
Trp
Tyr
Val
Asx
Glx
Sec
Unk
A
R
N
D
C
Q
E
G
H
I
L
K
M
F
P
S
T
W
Y
V
B
Z
U
X
Alanin e
Arginin e
Asparagin e
Aspartic acid
Cysteine
Glut amin e
Glut amic acid
Glycine
Histidin e
Isoleucine
Leucine
Lysine
Methionine
Phenylalanin e
Prolin e
Serin e
Threonine
Tryptophan
Tyrosine
Valin e
Asn or Asp
Gln or Glu
Selenocysteine
Unknown
Sperm whale myoglobin (1MBN)
Standard
Genetic
Code
Variation of genetic codes
T1
T2
T3
T4
T5
T6
T9
T10
T12
T13
T14
T15
CUU
CUC
CUA
CUG
Leu
Leu
Leu
Leu
-
Thr
Thr
Thr
Thr
-
-
-
-
-
Ser
-
-
-
AUU
AUC
AUA
AUG
Ile
Ile
Ile
Met
Met
-
Met
-
-
Met
-
-
-
-
-
Met
-
-
-
UAU
UAC
UAA
UAG
Tyr
Tyr
Stop
Stop
-
-
-
-
Gln
Gln
-
-
-
-
Tyr
-
Gln
AAU
AAC
AAA
AAG
Asn
Asn
Lys
Lys
-
-
-
-
-
Asn
-
-
-
-
Asn
-
-
UGU
UCG
UGA
UGG
Cys
Cys
Stop
Trp
Trp
-
Trp
-
Trp
-
Trp
-
-
Trp
-
Cys
-
-
Trp
-
Trp
-
-
AGU
AGC
AGA
AGG
Ser
Ser
Arg
Arg
Stop
Stop
-
-
Ser
Ser
-
Ser
Ser
-
-
Gly
Gly
Ser
Ser
-
T1: standard
T2: vert mt
T3: yeast mt
T4: other mt
T5: invert. mt
T6: cil. etc nuc.
T9: ech. mt
T10: eup. nuc.
T12:alt yeast nuc
T13: asc. mt
T14: flat. mt
T15: bleph. nuc.
The central dogma and its evolution
Transcription
Replication
DNA
Translation
RNA
Protein
Reversetranscription
(RNA World)
RNA
RNA
Schematic illustration of a eukaryotic cell
Schematic illustration of a plant cell
The dual flow of information in life:
the vertical flow by genetic information transmission, and
the horizontal flow by the genetic information expression
Development
Organism
Germ Cell Line
History of structure determination for nucleic acids and proteins
1950
Technology development
Structure determi nation
49 Edman degr adation
-heli x model
54 Isomorphou s replaceme nt
1960
53 DNA double heli x model
Insu li n p rim ary struc ture
60 Myog lobin tertiary structure
62 Restriction enzy me
65 tRNAAla prim ary struc ture
1970
72 DNA clon ing
73 tRNAPhe tertiary structure
75 DNA sequenc ing
77 X174 complete genom e
79 Z-DNA by s ingle crystal differentiation
1980
84 Puls e fi eld gel electrophoresis
85 Polymerase chain reaction
87 YAC vec tor
86 Protein structure by 2D NMR
88 Human Geno me Project
1990
93 DNA chip
95 H influenzae complete geno me
2000
DNA B-type (7BNA)
DNA A-type (140D)
DNA Z-type (2ZNA)
Polymorphic DNA tertiary structures
Yeast alanyl transfer RNA
Yeast phenylalanine tRNA (1TRA)
The information content of various species in terms of the number of nucleotides in the
genome. The complete genome sequences were determined in the years as designated.
The increase of the GenBank nucleotide sequence database is also shown together with
the release dates.
(Bit s)
232
109


(Nuc le otides)
Human
Mouse



Rice
Fruit F ly
Nematode (1998)


Arabidopsis
Budd ing yea st (1997)
224

Genbank 10/97

Gen Bank 9/92

Genbank 9/87

Gen Bank 10/82
107


Escherichia coli (1997)
Haemoph ilius influenzae (1995)

Cytomegalov ir us (1990)

phage (1982)

X174 phage (1977)
105
216
103
28
Human chromosomes: idiograms
Chromosomes
X-linked recessive disorder. The inheritance pattern is shown for
a recessive gene on the chromosome X, designated in bold.
Male
XY
(normal)
Male
XY
(normal)
Male
XY
(affected)
Female
XX
(normal)
Female
XX
(normal)
Female
XX
(normal)
Linkage analysis. The relative distance between the disease gene
(D) and a marker (M) can be estimated from the frequency
that both D and M are transmitted together to offspring.
Father
Mother
Marker M
Disease gene D
Children
M
D
M
M
D
D
Reductionistic and synthetic approaches in biology
Biological System
(Organism)
Reductionistic
Synthetic
Approach
Approach
(Experiments)
(Bioinformatics)
Building Blocks
(Genes/Molecules)
Basic principles in physics, chemistry and biology.
Principles Known?
Physics
Chemistry
Biology
Matter
Compound
Organism
Elementary
Particles
Elements
Genes
Yes
Yes
No
The Protein Folding Problem
Protein Folding Problem
(Sequence 3D Structure)
1 Protein folding is thermodynamically determined
(Anfinsen’s thermodynamic principle)
Protein + Environment
2. Protein folding is a reaction imvolving other
interacting molecules
(Principle of molecular interactions)
Protein + Chaperonins +….
Central Paradigm