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