Mathematical Modeling of Viral dynamics (HIV / Hepatitis) and Resistance Evolution
Viral Evolution and Recombination
description
Transcript of Viral Evolution and Recombination
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Phylogenetic analysis
• Reconstruction of
evolutionary history
• Relationship
• Distance
• Common ancestors
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Tree of Life
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Viruses and Viral Evolution
• Viruses are not living organisms!
• but evolving…
• Genetic material (DNA or RNA)
• Need to adapt to their environment!
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Different representations of phylogenetic trees
A B C D
ABCD
AB
C
D
A
BC
D
ABCD
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Bootstrap
-A way to get “statistical significance” of a certain topology
-Construct several new sequence sets (1000 st.)
-A new sequence set is generated by randomly picking of columns from the original set
-Apply the phylogenetic algorithm on all sets.
-Make one consensus tree from all trees
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BootstrappingA: AACTTAACCACGCTATCGATGCAATTATATAB: AATTTGACTGCGGTACCGATCCAATTATATAC: AATTTGACTGGGCTACCGATCCAATTATATAD: AACTTAACCGCGCTACTGATCGAATTATATA
A: CACCB: TGCTC: TGCTD: CAGC
A
D
B
C
96
96
A
B
C
D
3
3
A
C
B
D
1
1
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Recombination
• A powerful genetic mechanism
• Used by all animals (extremely few exceptions)
• Beneficial despite “the cost of sex”
• Speeds up evolution (up to 10,000 times)
• Accumulate beneficial mutations
• Expel deleterious mutations
• Bacteria through HGT
•Viruses!
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Recombination
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Recombination and phylogeny
X
A
B
C
D
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FG
H
I
A
B
C
D
E
FG
H
I
H
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Recombination and phylogeny
X
A
B
C
D
E
FG
H
I
H
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Phylogenetic networks
X
A
B
C
DE
FG
H
I
H
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Methods for detection of recombinants
-Detecting conflicting phylogenetic signals
•Phylogenetic networks (SplitsTree)
•Can be due to recombination or homoplasy
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Phylogenetic network
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Methods for detection of recombinants
-Analyze conflicting phylogenetic signals, recombination vs homoplasy, and define breakpoints
•Bootscan (SimPlot)
•Similarity plots (SimPlot)
•Statistical tests (phi-test)
•RDP, Geneconv, MaxChi, Chimaera, SisScan, 3Sec, LARD, Topal, …. (RDP)
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Bootscan