Download LecCh3Alignment

Alignments

Why do Alignments?
Detecting
Selection
Evolution of
Drug Resistance in HIV
Selection on Amino Acid
Properties


TreeSAAP (2003)
Wu Method (Sainudiin et al. 2005)
TreeSAAP Properties















Alpha-helical tendencies
Average number of surrounding
residues
Beta-structure tendencies
Bulkiness
Buriedness
Chromatographic Index
Coil tendencies
Composition
Compressibility
Equilibrium constant (ionization of
COOH)
Helical contact area
Hydropathy
Isoelectric point
Long-range non-bonded energy
Mean r.m.s. fluctuation displacement
















Molecular volume
Molecular weight
Normalized consensus hydrophobicity
Partial specific volume
Polar requirement
Polarity
Power to be at the C-terminal
Power to be at the middle of alphahelix
Power to be at the N-terminal
Refractive index
Short and medium range non-bonded
energy
Solvent accessible reduction ratio
Surrounding hydrophobicity
Thermodynamic transfer
hydrophobicity
Total non-bonded energy
Turn tendencies
TreeSAAP
Rhinoviruses
Selected
Sites
3D Mapping
OPSIN: Model System for Molecular Evolution
UV
IR
400
500
600
700
Wavelength (nm)
ENVIRONMENT
CRLAKIAMTTVALWFIAWT
PYLLINWVGMFARSYLSPV
YTIWGYVFAKANAVYNPIV
YAISHPKYRAAMEKKLPCL
SCKTESDDVSESASTTTSS
GENOTYPE
PHENOTYPE
Is max Correlated with Ecological
Differences?
INPUT
OUTPUT
microscopic thin beam of spectral light
Detect light not absorbed
by the photopigment
INPUT – OUTPUT = pigment absorbance
400 – 700 nm at 1nm intervals
Invertebrate Opsin Evolution
PHYML
amino acid
ML tree
Heliconius erato
Heliconius sara
Bicyclus anynana
Junonia coenia
Vanessa cardui
Papilio xuthus Rh1
Papilio xuthus Rh3
Pieris rapae
Manduca sexta
Insect LWS
Galleria mellonella
Spodoptera exigua
508-575 nm
Papilio xuthus Rh2
Osmia rufa
Bombus terretsris
Apis mellifera
Camponotus abdominalis
Cataglyphis bombycinus
Schistocerca gregaria
Sphrodromantis sp.
Drosophila melanogaster Rh6
Drosophila melanogaster Rh1 Insect MWS
Calliphora erythrocephala Rh1
Drosophila melanogaster Rh2
Neogonodactylus oerstedii Rh3 420-490 nm
Neogonodactylus oerstedii Rh1
Neogonodactylus oerstedii Rh2
Homarus gammarus
Neomysis americana
Holmesimysis costata
Crustacean LWS
Procambarus milleri
Orconectes virilis
496-533 nm
Procambarus clarkii
Cambarus ludovicianus
Cambarellus schufeldtii
Euphausia suberba
Mysis relicta sp.IV
Archaeomysis grebnitzkii
Limulus polyphemus
Chelicerate LWS (520)
Limulus polyphemus
Hemigrapsus sanguineus
Crustacean MWS (480)
Hemigrapsus sanguineus
Camponotus abdominalis
Cataglyphis bombycinus
Apis mellifera
Insect UV
Manduca sexta
Papilio xuthus Rh5
345-375nm
Drosophila melanogaster Rh4
Drosophila melanogaster Rh3
Apis mellifera
Schistocerca gregaria
Insect BL
Papilio xuthus Rh4
Manduca sexta
Drosophila melanogaster Rh5 430-460nm
Loligo pealii
Loligo forbesi
Loligo subulata
Cephalopod Rh
Sepia officinalis
Todarodes pacificus
480-499nm
Enteroctopus dofleini
Gallus gallus pineal
Anolis carolinensis pineal
Bos taurus rhodopsin
Homo sapiens melatonin 1A
Homo sapiens GPR52
0.1
Thicker
Thickbranches
branchesindicate
indicatebootstrap
bootstrapvalues
values>>90%
Coil Tendencies, Compressibility,
Alpha-Helix
TreeSAAP
6
TMII
TMI
TMIII
TMIV
TMV
TMVI
Coil Tendencies
4
2
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190
200
210
220
230
240
250
260
60
70
80
90
100
110
120
130
140
150
160
170
180
190
200
210
220
230
240
250
260
-2
6
Compressibility
4
2
Z-score
0
10
20
30
40
50
-2
6
Power to be at mid alpha
4
2
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190
200
210
220
230
240
250
260
60
70
80
90
100
110
120
130
140
150
160
170
180
190
200
210
220
230
240
250
260
-2
10
Refractive Index
8
6
4
2
0
0
10
20
30
40
50
-2
Amino acid alignment number
Invertebrate Opsin Evolution
PHYML
amino acid
ML tree
Heliconius erato
Heliconius sara
Bicyclus anynana
Junonia coenia
Vanessa cardui
Papilio xuthus Rh1
Papilio xuthus Rh3
Pieris rapae
Manduca sexta
Insect LWS
Galleria mellonella
Spodoptera exigua
508-575 nm
Papilio xuthus Rh2
Osmia rufa
Bombus terretsris
Apis mellifera
Camponotus abdominalis
Cataglyphis bombycinus
Schistocerca gregaria
Sphrodromantis sp.
Drosophila melanogaster Rh6
Drosophila melanogaster Rh1 Insect MWS
Calliphora erythrocephala Rh1
Drosophila melanogaster Rh2
Neogonodactylus oerstedii Rh3 420-490 nm
Neogonodactylus oerstedii Rh1
Neogonodactylus oerstedii Rh2
Homarus gammarus
Neomysis americana
Holmesimysis costata
Crustacean LWS
Procambarus milleri
Orconectes virilis
496-533 nm
Procambarus clarkii
Cambarus ludovicianus
Cambarellus schufeldtii
Euphausia suberba
Mysis relicta sp.IV
Archaeomysis grebnitzkii
Limulus polyphemus
Chelicerate LWS (520)
Limulus polyphemus
Hemigrapsus sanguineus
Crustacean MWS (480)
Hemigrapsus sanguineus
Camponotus abdominalis
Cataglyphis bombycinus
Apis mellifera
Insect UV
Manduca sexta
Papilio xuthus Rh5
345-375nm
Drosophila melanogaster Rh4
Drosophila melanogaster Rh3
Apis mellifera
Schistocerca gregaria
Insect BL
Papilio xuthus Rh4
Manduca sexta
Drosophila melanogaster Rh5 430-460nm
Loligo pealii
Loligo forbesi
Loligo subulata
Cephalopod Rh
Sepia officinalis
Todarodes pacificus
480-499nm
Enteroctopus dofleini
Gallus gallus pineal
Anolis carolinensis pineal
Bos taurus rhodopsin
Homo sapiens melatonin 1A
Homo sapiens GPR52
0.1
Thicker
Thickbranches
branchesindicate
indicatebootstrap
bootstrapvalues
values>>90%
Homology
Homology definitions




Homology is an evolutionary relationship that
either exists or does not. It cannot be partial.
An ortholog is a homolog that arose through a
speciation event
A paralog is a homolog that arose through a
gene duplication event. Paralogs often have
divergent function.
Similarity is a measure of the quality of
alignment between two sequences. High
similarity is evidence for homology. Similar
sequences may be orthologs or paralogs.
One More Homology type


Xenology – similarity due to horizontal
gene transfer (HGT)
How do you discover this?
Alignment Problem


(Optimal) pairwise alignment consists of
considering all possible alignments of
two sequences and choosing the
optimal one.
Sub-optimal (heuristic) alignment
algorithms are also very important: eg
BLAST
Key Issues




Types of alignments (local vs.
global)
The scoring system
The alignment algorithm
Measuring alignment significance
Types of Alignment




Global—sequences aligned from endto-end.
Local—alignments may start in the
middle of either sequence
Ungapped—no insertions or deletions
are allowed
Other types: overlap alignments,
repeated match alignments
Local vs. Global
Pairwise Alignments

A global alignment includes all elements of
the sequences and includes gaps.



A global alignment may or may not include "end
gap" penalties.
Global alignments are better indicators of
homology and take longer to compute.
A local alignment includes only
subsequences, and sometimes is computed
without gaps.

Local alignments can find shared domains in
divergent proteins and are fast to compute
How do you compare
alignments?

Scoring scheme

What events do we score?






Matches
Mismatches
Gaps
What scores will you give these events?
What assumptions are you making?
Score your alignment
Scoring Matrices



How do you determine scores?
What is out there already for your use?
DNA versus Amino Acids?


TTACGGAGCTTC
CTGAGATCC
Multiple Sequence Alignment

Global versus Local Alignments
Progressive alignment
Estimate guide tree
 Do pairwise alignment on subtrees
ClustalX

Improvements

Consistency-based Algorithms

T-Coffee - consistency-based objective
function to minimize potential errors



Generates pair-wise global (Clustal)
Local (Lalign)
Then combine, reweight, progressive alignment
Iterative Algorithms




Estimate draft progressive alignment
(uncorrected distances)
Improved progressive (reestimate guide
tree using Kimura 2-parameter)
Refinement - divide into 2 subtrees,
estimate two profiles, then re-align 2
profiles
Continue refinement until convergence
Software




Clustal
T-Coffee
MUSCLE (limited models)
MAFFT (wide variety of models)
Comparisons

Speed


Accuracy


Muscle>MAFFT>CLUSTALW>T-COFFEE
MAFFT>Muscle>T-COFFEE>CLUSTALW
Lots more work to do here!