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Transcript of Blueprint of Life Based on Chapter 1 of Post-genome Informatics by Minoru Kanehisa, Oxford...
Blueprint of Life
Based on Chapter 1 of Post-genome Informatics
by Minoru Kanehisa,
Oxford University Press, 2000
Genome and gene
Entity Definition Molecular MechanismsGenome Unit of information transmission DNA replication
Gene Unit of information expression Transcription to RNATranslation to protein
Nucleic acid and proteins
Macromolecule Backbone Repeating unit Length Role
DNA Phosphodiester bonds Deoxyribonucleotides(A, C, G, T)
103-108 Genome
Nucleicacid RNA Phosphodiester bonds Ribonucleotides
(A, C, G, U)103-105
103-104
102-103
GenomeMessengerGene product
Protein Peptide bonds Amino acids(A, C, D, E, F, G, H,I, K, L, M, N, P, Q,R, S, T, V, W, Y)
102-103 Gene product
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 Pyrimidine (C or T) D Not C (A or G or T)
N Any nucleotide V Not T (A or G or C)
AdenineGuanine
Thymine Cytosine Uracil
BASES
The Four Nucleosides of DNA
dA dG dC dT
A nucleoside is a sugar, here deoxyribose, plus a base
dA = deoxyadenosine, etc.
PYRIMIDINESPURINES
Base Pairing
A nucleotide is a phospate, a sugar, and a purine or a pyramidine base.
The monomeric units of nucleic acids are called nucleotides.
DNA: B form (7BNA)
Amino acid codes
AlaArgAsnAspCysGlnGluGlyHisIleLeuLysMetPheProSerThrTrpTyrVa lAsxGlxSecUnk
ARNDCQEGHILKMFPSTWYVBZUX
AlanineArginineAsparagineAspartic acidCysteineGlutamineGlutamic acidGlycineHistidineIsoleucineLeucineLysineMethioninePhenylalanineProlineSerineThreonineTryptophanTyrosineVa lineAsn or AspGln or GluSelenocysteineUnknown
Sperm whale myoglobin (1MBN)
StandardGenetic
Code
Variation of genetic codes
T1 T2 T3 T4 T5 T6 T9 T10 T12 T13 T14 T15
CUUCUCCUACUG
LeuLeuLeuLeu
----
ThrThrThrThr
----
----
----
----
----
---Ser
----
----
----
AUUAUCAUAAUG
IleIleIleMet
--Met-
--Met-
----
--Met-
----
----
----
----
--Met-
----
----
UAUUACUAAUAG
TyrTyrStopStop
----
----
----
----
--GlnGln
----
----
----
----
--Tyr-
---Gln
AAUAACAAAAAG
AsnAsnLysLys
----
----
----
----
----
--Asn-
----
----
----
--Asn-
----
UGUUCGUGAUGG
CysCysStopTrp
--Trp-
--Trp-
--Trp-
--Trp-
----
--Trp-
--Cys-
----
--Trp-
--Trp-
----
AGUAGCAGAAGG
SerSerArgArg
--StopStop
----
----
--SerSer
----
--SerSer
----
----
--GlyGly
--SerSer
----
T1: standardT2: vert mtT3: yeast mtT4: other mtT5: invert. mtT6: cil. etc nuc.T9: ech. mtT10: eup. nuc.T12:alt yeast nucT13: asc. mtT14: flat. mtT15: bleph. nuc.
The central dogma and its evolution
Replication
Transcription
DNA
Reverse-transcription
RNA
Translation
Protein
(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 proteinsTechnology development Structure determination
195049 Edman degradation
54 Isomorphous replacement
51 α-heli xmodel
53 DNA double heli xmodelInsuli n primar ystructure
1960
62 Restricti onenzyme
60 Myoglobi ntertiar ystructure
65 tRNAAla primar ystructure
1970
72 DNA cloning
75 DNA sequencing
73 tRNAPhe tertiar ystructure
77 φ 174X complet e genome
79 Z-DNA by single crysta l differentiation1980
84 Puls efiel d gel electrophoresis85 Polymerase chai nreaction
87 YAC vector86 Protei nstructure 2by D NMR
88 Hum an Genome Project
1990
93 DNA chip
95 H influenzae complet e genome
2000
DNA A-type (140D)DNA B-type (7BNA) 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.
(Bits) (Nucleotides)232
224
109• Human• Mouse
• Rice• Fruit Fly• Nematode (1998)
• Arabidopsis• Budding yeast (1997)
• Genbank 10/97
• GenBank 9/92
• Genbank 9/87107
• Escheri chia coli (1997)• Haemophili us influenzae (1995)
• Cytomegalovirus (1990)
• GenBank 10/82
216105
• λ phage (1982)
• φX174 phage (1977)
28
103
Human chromosomes: idiograms
Chromosomes
X-linked recessive disorder. The inheritance pattern is shown for a recessive gene on the chromosome X, designated in bold.
MaleXY
(normal)
FemaleXX
(normal)
Female XX(normal)
Female XX(normal)
Male XY(normal)
Male XY(affected)
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
Children
Marker M
Disease gene D
M
D
M M
D D
Reductionistic and synthetic approaches in biology
Biological System
(Organism)
Building Blocks
(Genes/Molecules)
Synthetic
Approach
(Bioinformatics)
Reductionistic
Approach
(Experiments)
Basic principles in physics, chemistry and biology.
Principles Known?
Physics
Matter
Chemistry
Compound
Biology
Organism
ElementaryParticles
Yes
Elements
Yes
Genes
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