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Flow of Genetic Information
A Montagud
E Navarro
P Fernández de Córdoba
JF Urchueguía
presents
Flow of Genetic Information
Elements
Nucleic acidDNA
building block
structure & organization
genome
RNAbuilding block
types
Amino acidbuilding block
side chainprotein
Central Dogma of Molecular Biology
Replication : DNA to DNA
Replication : RNA to RNATranscription : DNA to RNA
RNA processing
Translation : RNA to proteingenetic code
Dogma, revisited
Horizontal transferencetransformationconjugation
transduction
Flow of Genetic Information
Elements
two monomers and two polymersnucleic acids
DNA : stores information
RNA : transmits information
amino acidsprotein : catalytic capacity
Nucleic acids
Flow of Genetic Information
Nucleic acid : DNA
main functionstore information
Flow of Genetic Information
Figure 4‐3. DNA and its buildingblocks. (Alberts et al, 2002)
Flow of Genetic Information
double helix
minor groove
major groove
structure and organization
A‐DNA B‐DNA Z‐DNA
more compact left‐handed
Flow of Genetic Information
Figure 4‐55.Chromatin
packing(Alberts et al,
2002)
chromatin : supercoiling
chromosome
Flow of Genetic Information
genome
whole genetic material necessary for thesurvival of a given cell
humans
bacteria
Flow of Genetic Information
genome : chromosomes
Flow of Genetic Information
genome : plasmids
autonomous genetic elements
not essential –(generally) bacteria survives without
interesting properties survival on a special condition
pathogenicity island
characteristic copy number
Flow of Genetic Information
Nucleic acid : RNA
Krogh, 2004
Flow of Genetic Information
microRNA, has been shown to regulate gene expression.
Krogh, 2004
Amino acids
Flow of Genetic Information
Amino acid : building block
Flow of Genetic Information
Amino acid : side chain
Flow of Genetic Information
2ary structurealpha helix
beta sheet
3ary structuredomains
Amino acid : protein
The sequence of amino acids determines the
structure, and therefore the function, of a protein.
Figure 3‐9. Theregular
conformation ofthe polypeptide
backbone observedin the α helix and
the β sheet. (Alberts et al, 2002)
Flow of Genetic Information
Figure 7‐17. One type of zinc finger protein.(Alberts et al, 2002)
beta sheet
alpha helix
Amino acid : examples
Figure 7‐115. A comparison ofthe structure of one‐chain and
four‐chain globins.(Alberts et al, 2002)
Flow of Genetic Information
Amino acid : protein and function
Figure 3‐6. How a protein folds into a compact conformation.
(Alberts et al, 2002)
Figure 6‐82. A current view of protein folding. (Alberts et al,
2002)
Correct folding is critical for correct function
Central Dogma of Molecular Biology
Flow of Genetic Information
Central Dogma of Molecular Biology
Francis Crick, Ideas onprotein synthesis. SympSoc Exp Biol., 1956
DNA
RNA
protein
translation
transcription
replication
replication
Flow of Genetic Information
Replication : DNA to DNA
DNA polymerase DNA dependent
DNA nucleotides
many enzymes more!helicase, topoisomerase, etc
Figure 7‐2. Plasmid DNA replication. (Lodish et al, 2000)
DNA
RNA
protein
translation
transcription
replication
replication
DNA
RNA
protein
translation
transcription
replication
replication
Flow of Genetic Information
Figure 5.11.Model ofthe E. coli replicationfork. (Cooper, 2000)
Figure 5‐4. DNA synthesis catalyzed by DNA polymerase. (Alberts et al, 2002)
Flow of Genetic Information
Figure 12‐9. At a growing fork, onestrand is synthesizedfrom multiple primers. (Lodish et al, 2000)
Figure 5‐12. RNA primer synthesis. (Albert et al, 2002)
primase(RNA pol DNA
dep)
Flow of Genetic Information
movie : replication
Ch12anim1. Lodish et al, 2000
Flow of Genetic Information
RNA polymerase RNA dependent
RNA viruseshave RNA as information
storage
live in the RNA world
use cell machinery
Replication : RNA to RNADNA
RNA
protein
translation
transcription
replication
replication
DNA
RNA
protein
translation
transcription
replication
replication
Flow of Genetic Information
Transcription : DNA to RNA
RNA polymerase DNA dependent
RNA nucleotides
many enzymes more!helicase, topoisomerase, etc
transcription factors : regulation
DNA
RNA
protein
translation
transcription
replication
replication
DNA
RNA
protein
translation
transcription
replication
replication
Flow of Genetic Information
Figure 6‐7. DNA transcriptionproduces a single‐stranded RNA molecule that is complementaryto one strand of DNA. (Alberts et al, 2002)
Flow of Genetic Information
movie : transcription
Ch4anim1. Lodish et al, 2000
Flow of Genetic Information
RNA processing
mRNA gets processed, mainly in eukaryotes
5’‐capping
protection from degradation
Figure 6‐22. A comparison of the structures ofprocaryotic and eucaryotic mRNA molecules.
(Alberts et al, 2002)
DNA
RNA
protein
translation
transcription
replication
replication
DNA
RNA
protein
translation
transcription
replication
replication
Flow of Genetic Information
RNA processing
mRNA gets processed, mainly in eukaryotes
splicing
Krogh, 2004
Flow of Genetic Information
RNA processing
mRNA gets processed, mainly in eukaryotes
alternative splicing
Krogh, 2004
Flow of Genetic Information
RNA processing
mRNA gets processed, mainly in eukaryotes
3’‐polyadenylationprotection from degradation
Figure 6.40. Formation ofthe 3 ′ ends of eukaryoticmRNAs. (Cooper, 2000)
Flow of Genetic Information
RNA processing
mRNA gets processed, mainly in eukaryotes5’‐capping
splicing, alternative splicing
3’‐polyadenylation
Figure 11‐7. Overview ofmRNA processing in
eukaryotes. (Lodish et al, 2000)
DNA
RNA
protein
translation
transcription
replication
replication
DNA
RNA
protein
translation
transcription
replication
replication
Flow of Genetic Information
movie : RNA processing
Ch11anim1. Lodish et al, 2000
Flow of Genetic Information
Translation : RNA to protein
mRNA
ribosomes
tRNA
amino acids
DNA
RNA
protein
translation
transcription
replication
replication
DNA
RNA
protein
translation
transcription
replication
replication
Krogh, 2004
Flow of Genetic Information
Translation : RNA to protein
Krogh, 2004
Flow of Genetic Information
Translation : genetic code
Krogh, 2004
Flow of Genetic InformationKrogh, 2004
Flow of Genetic Information
from DNA to protein
DNA
RNA
protein
5’UTR 3’UTR3’5’
promoter
AAAAACDSSTART STOP
intron intron intron
DNA
RNA
protein
translation
transcription
replication
replication
DNA
RNA
protein
translation
transcription
replication
replication
Flow of Genetic Information
movie : traduction
Ch4anim3. Lodish et al, 2000
Dogma, revisited
Flow of Genetic Information
Dogma, revisited
As it turned out, the use of the word dogmacaused almost more trouble than it wasworth.... I used the word the way I myselfthought about it, not as most of the worlddoes, and simply applied it to a grandhypothesis that, however plausible, hadlittle direct experimental support.
‐Francis Crick, What Mad Pursuit, 1988
DNA
RNA
protein
translation
transcription
replication
replication
Flow of Genetic Information
DNA reverse transcriptaseretroviruses
Dogma, revisited
Figure 5‐73. The lifecycle of a retrovirus. (Alberts et al, 2002)
DNA
RNA
protein
translation
transcription
replication
replication
DNA
RNA
protein
translation
transcription
replication
replication
Flow of Genetic Information
DNA reverse transcriptasetelomeres
Dogma, revisited
Figure 5‐44. The t‐loopsat the end of mammalian
chromosomes.(Alberts et al, 2002)
Figure 5‐43. Telomere replication. (Alberts et al, 2002)
DNA
RNA
protein
translation
transcription
replication
replication
DNA
RNA
protein
translation
transcription
replication
replication
Flow of Genetic Information
movie : telomerase
Ch12anim5. Lodish et al, 2000
Flow of Genetic Information
prions
Dogma, revisited
Figure 6‐89. Proteinaggregates that cause
human disease. (Alberts et al, 2002)
DNA
RNA
protein
translation
transcription
replication
replication
DNA
RNA
protein
translation
transcription
replication
replication
Flow of Genetic Information
Dogma, revisited
Crick, Central Dogma of Molecular Biology, Nature, 1970
DNA
RNA
protein
translation
transcription
replication
reverse transcription
protein aggregation
replication
Flow of Genetic Information
Dogma’s overview
static
stepwise
simplistic
Flow of Genetic Information
Dogma’s overview
dynamic
continuousreactions
complex
Flow of Genetic Information
transcription and translation
Figure 28.15. Transcription and Translation. (Berg et al, 2002)
Horizontal transference
Flow of Genetic Information
Horizontal transference
special in prokaryotes
transformation
conjugation
transduction
Flow of Genetic Information
Horizontal transference
conjugationF plasmid & tra genes
pilus
Figure 7‐35.(Griffiths et al, 2000)
Flow of Genetic Information
Horizontal transference
transformationbacteria recombines free DNA as its own
Figure 7‐35.(Griffiths et al, 2000)
Flow of Genetic Information
Horizontal transference
transductionphage lysis
phage encapsulates bacterial DNA
Figure 7‐35.(Griffiths et al, 2000)
Flow of Genetic Information
more
vcell.ndsu.edutranscription
mRNA processing
Flow of Genetic Information
sourcesAlberts et al, Molecular Biology of the Cell, Garland Science, 4th ed, 2002
Lodish et al, Molecular Cell Biology, Freeman & Co., 4th ed., 2000
Griffiths et al, Introduction to Genetic Analysis, Freeman & Co., 7th ed, 2000
Berg et al, Biochemistry, Freeman & Co., 5th ed., 2002
Crick, Ideas on Protein Synthesis, Symp Soc Exp Biol, 1956
Crick, Central Dogma of Molecular Biology, Nature, 1970
Crick, What Mad Pursuit: a personal view of scientific discovery, BasicBooks, 1990