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Linköping University & Karolinska Institutet 2010-03-17
(c) Bengt Persson 1
Bengt Persson
Evolution 109 years ago
General evolutionary tree
archaea
Linköping University & Karolinska Institutet 2010-03-17
(c) Bengt Persson 2
Natural selection
“Survival of the fittest”, Darwin
Nucleotide substitutions
Frequence of mutationsFixation in populationVariation dependent on:– gene / not gene– site in gene– which gene
Linköping University & Karolinska Institutet 7
Rates of evolution in different proteins
Protein Rate (changes in 109 years) Fibrinopeptides 8.3 Lysozyme 2.0 α-Globin 1.2 Insulin 0.44 Cytochrome c 0.3 Histone H4 0.01
from Ridley: Evolution
Constant speed of change for a certain gene in all species (Molecular clock)
Linköping University & Karolinska Institutet 8
from Ridley: EvolutionThe rate of evolution of α-globin.
Constant evolutionary speed
Linköping University & Karolinska Institutet 2010-03-17
(c) Bengt Persson 3
Increase of genome size
1. Genome duplicationstetraploid organisms
2. Regional duplicationsa) internally in genes
Examples: collagen, immunoglobulinb) gene duplications
Examples: rRNA genes, lactalbumin & lysozyme, gene families (globins, immunoglobulins), pseudogenes
Genome sizes (from Dayhoff, 1972)
Effects of gene duplications
Same function in a new context– e.g. lysozymeExtended physiological repetoire– e.g. globin
Evolutionary tree, hemoglobin
Linköping University & Karolinska Institutet 2010-03-17
(c) Bengt Persson 4
Linköping University & Karolinska Institutet 13
Domains
Linköping University & Karolinska Institutet 14
Modular architecture 1
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Modular architecture 2
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Conserved folds
Linköping University & Karolinska Institutet 2010-03-17
(c) Bengt Persson 5
Linköping University & Karolinska Institutet 17
Glycine conserved at turns
Linköping University & Karolinska Institutet 18
Evolution of active site
Linköping University & Karolinska Institutet 19
Mutations and diseaseAltered exterior– normally harmless but might cause disease– e.g. Hemoglobin SAltered active site– often critical, e.g. change of substrate specificityAltered tertiary structure– e.g. unstable forms(Hb Riverdale‐Bronx with G‐>R mutation)
Altered quaternary structure– change of allosteric properties
1
2
Linköping University & Karolinska Institutet 20
Location of mutations in Hb
2 1
Linköping University & Karolinska Institutet 2010-03-17
(c) Bengt Persson 6
Linköping University & Karolinska Institutet 21
Hb S aggregation
Linköping University & Karolinska Institutet 22
Hb S – Sickle cell anemia
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Three kingdoms
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from Ridley: Evolution
What to compare?
Linköping University & Karolinska Institutet 2010-03-17
(c) Bengt Persson 7
Linköping University & Karolinska Institutet 25
1
2
3
4
1
2
3
4
1
3
2
4
1
4
2
3
1 Ala2 Ser3 Ala4 Ser
A AA
S
S SA
A ASS S2 1 2
Parsimony
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Number of unrooted trees
from Meth. Enzymol. 183
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HomologyProperty of several species also present in common ancestor
Divergent evolution
AnalogyProperty of several species not present in common ancestor
Convergent evolution
The terms homology and analogy
Linköping University & Karolinska Institutet 28
Programs for tree calculations
ClustalW– distance method Des HigginsPhylip/Protpars– parsimony Joe FelsensteinTree, Papa etc.– progressive alignments Russ Doolittle– followed by parsimony
Linköping University & Karolinska Institutet 2010-03-17
(c) Bengt Persson 8
Linköping University & Karolinska Institutet 29
ClustalW − main menu********************************************************************** CLUSTAL W(1.5) Multiple Sequence Alignments **********************************************************************
1. Sequence Input From Disc2. Multiple Alignments3. Profile Alignments4. Phylogenetic trees
S. Execute a system commandH. HELPX. EXIT (leave program)
Your choice: 1
Sequences should all be in 1 file.
6 formats accepted: NBRF/PIR, EMBL/SwissProt, Pearson (Fasta), GDE, Clustal, GCG/MSF.Enter the name of the sequence file:
Linköping University & Karolinska Institutet 30
Phylogenetic tree menu1. Input an alignment
2. Exclude positions with gaps? = OFF3. Correct for multiple substitutions? = OFF
4. Draw tree now
5. Bootstrap tree
6. Output format options
S. Execute a system command
H. HELPor press [RETURN] to go back to main menu
Your choice:
Linköping University & Karolinska Institutet 31
Phylogenetic tree file(
(
((
(ADH1_ALLMI:0.09794,
(
(ADH1_APTAU:0.03428,
ADH1_STRCA:0.03000)971:0.02669,
ADH1_CHICK:0.07911)
995:0.03574)899:0.01605,
. . .
. . .
(
((
(ADHA_HUMAN:0.02645,
ADH_MACMU:0.03491)
672:0.00793,ADHB_HUMAN:0.02422)
862:0.01244,ADHG_HUMAN:0.02419)
999:0.03896,
ADHE_HORSE:0.06256)675:0.00839)
700:0.01223)TRICHOTOMY;
Linköping University & Karolinska Institutet 32