Transcript Evolutionary relationships

Evolutionary relationships
and
finding new drugs in daffodils
1) Constructing phylogenies (working out evolutionary
relationships)
a) Why constructing phylogenies (or understanding evolutionary
relationships) is important.
b) How phylogenies are constructed.
2) Using phylogenies to help in the search for new drugs
a) Creating a useful phylogeny.
b) Choosing species to investigate.
Why constructing phylogenies (or understanding
evolutionary relationships) is important.
Look at these 3 articles and use your own thoughts to explain
why scientists may be interested in understanding
evolutionary relationships.
Why constructing phylogenies
(or understanding evolutionary
relationships) is important
How phylogenies are constructed
An example of a phlogenetic tree
Gorillas
Humans
Chimpanzees
How many possible trees for 3 species?
How many possible trees for 3 species?
C
A
B
B
A
C
A
B
C
So there are 3
possible trees
for 3 species
How many possible trees for 4 species?
How many possible trees for 4 species?
D
D
D
C
C
C
B
B
B
A
A
A
C
B
A
D
B
A
D
C
A
D
C
B
A
A
B
A
A
B
A
A
C
B
B
C
B
C
C
B
D
D
C
D
D
C
D
D
So there are 12 of one
shape and 3 of another
making 15 possible trees
overall for 4 species
A
A
A
D
C
B
B
B
C
C
D
D
Choosing the most likely evolutionary tree
1. Identifying evolutionary change in Amino acids
1. Galanthus nivalis (Common snowdrop)
2. Narcissus cernuus
3. Narcissus tazetta
4. Narcissus asturiensis
1a.
2a.
3a.
4a.
INRNLLLSTM
VNRNLLLSTM
VNRNLLLSTM
VNRNLLLSTM
NNKVSFFSKD
NNRVSFFSKD
NNKVSFFSKD
NNRVSFFSKD
IYRIDDNVRN
IYRIDDNVRN
IYRIDDNVRN
IYRIDDNVRN
RVRYFSTYFR
GVRDFSTYFR
GVRYFSTYFR
GVRYFSTYFR
NKYTCTYPHE
NKYTYTHPHE
NKYTYTYPHE
NKYTYTHPHE
SDNTMLFPLL
SDNTMLFPLL
SDNTMLFPLL
SDNTMLFPLL
VLGLFTLFIG
VLVLFPLFIG
VLVLFTLFIG
VLVLFTLFIG
1b.
2b.
3b.
4b.
SKDSSDWYEF
AKDSSDWCEF
SKDSSDWYEF
AKDSSDWCEF
LKNVVFSVSI
LKNAVFSVSI
LKNAVFSVSI
LKNAVFSVSI
ALFGLFVASI
ALFGLFVASI
ALFGLFVASI
ALFGLFVASI
LYGSVYSSLQ
LYGSVYSSLQ
FYGSVYSSLQ
LYGSVYSSLQ
NLGLVNSFVK
NLGLVNSFVK
NLGLVNSFVK
NLGLVNSFVK
KSPKRILLDQ
KSPKRILLDQ
KSPKRILLDQ
KNPKRILLDQ
VK
AQ
VK
VQ
AIGIHFDRGV
AIGIHFDLGV
AIGIHFDRGV
AIGIHFDRGV
IDFDLLSKWI
IDFDLLSKWL
IDFDLLSKWL
IDFDLLSKWL
TPYADFFHPN
TPSADFFHPN
TPSADFFHPN
TPPADFFHPN
Choosing the most likely evolutionary tree
2. Mapping characters onto possible evolutionary
trees
93 S→P
93 S→P
Narcissus cernuus
Narcissus asturiensis
Narcissus tazetta
All orange characters
(positions 1, 31, 45, 63
and 114) occur once each
on all trees on the
Narcissus branch just after
G. nivalis branches off.
93 Y→S
Galanthus nivalis
93 Y→S
A
Narcissus tazetta
Narcissus cernuus
Narcissus asturiensis
Galanthus nivalis
Narcissus tazetta
Narcissus asturiensis
Narcissus cernuus
Galanthus nivalis
All blue characters
(positions 13, 47, 101,
108 and 162) occur
once each on tree C but
have to occur twice
each on trees A and B.
93 S→P
93 Y→S
C
B
All yellow characters
occur once each on
all trees. Positions 34,
66, 68 and 161 at the
tip where N. cernuus
is. Position 131 at the
tip where N. tazetta is.
Position 152 at the tip
where N. asturiensis
is.
Identifying the informative characteristics
Identifying the informative characteristics
Number in
the key
Description of amino acid
variation
Informative
characteristic?
1 (Green)
All amino acids the same
No
2 (Orange)
Amino acid only common to all
3 Narcissus species
No
3 (Yellow)
Amino acid different in only
one Narcissus species
No
4 (Blue)
2 species have one amino acid
and the other 2 have a
different one
Yes
5 (White)
Position 93
No
The informative ones are
shared, derived characteristics
Creating a useful phylogeny
Amino acid at each position number
Species
13
34
47
75
78
93
101
108
112
131
142
152
162
Galanthus nivalis (Common snowdrop) =
outgroup
K
Y
Y
H
R
Y
S
Y
K
L
L
S
K
Narcissus asturiensis
R
Y
H
H
R
P
A
C
K
L
L
N
Q
Narcissus atlanticus
K
Y
Y
R
R
S
S
C
K
L
F
S
K
Narcissus calcicola
K
Y
Y
H
R
S
S
C
K
L
F
S
K
Narcissus cernuus
R
D
H
H
L
S
A
C
K
L
L
S
Q
Narcissus jacetanus
R
Y
H
H
R
P
A
C
K
L
L
N
Q
Narcissus longispathus
K
Y
Y
H
R
S
A
C
Q
L
L
S
Q
Narcissus nevadensis
K
Y
Y
H
R
S
A
C
Q
L
L
S
Q
Narcissus pseudonarcissus
R
Y
H
H
R
S
A
C
K
L
L
N
Q
Narcissus scaberulus
K
Y
Y
R
R
S
S
C
K
L
F
S
K
Narcissus serotinus
K
Y
Y
H
R
S
S
Y
K
F
L
S
K
Narcissus tazetta
K
Y
Y
H
R
S
S
Y
K
F
L
S
K
Narcissus triandrus
R
D
H
H
L
S
A
C
K
L
L
S
Q
Amino acid at each position number
Species
13
34
47
75
78
93
101
108
112
131
142
152
162
Galanthus nivalis (Common snowdrop) =
outgroup
K
Y
Y
H
R
Y
S
Y
K
L
L
S
K
Narcissus asturiensis
R
Y
H
H
R
P
A
C
K
L
L
N
Q
Narcissus atlanticus
K
Y
Y
R
R
S
S
C
K
L
F
S
K
Narcissus calcicola
K
Y
Y
H
R
S
S
C
K
L
F
S
K
Narcissus cernuus
R
D
H
H
L
S
A
C
K
L
L
S
Q
Narcissus jacetanus
R
Y
H
H
R
P
A
C
K
L
L
N
Q
Narcissus longispathus
K
Y
Y
H
R
S
A
C
Q
L
L
S
Q
Narcissus nevadensis
K
Y
Y
H
R
S
A
C
Q
L
L
S
Q
Narcissus pseudonarcissus
R
Y
H
H
R
S
A
C
K
L
L
N
Q
Narcissus scaberulus
K
Y
Y
R
R
S
S
C
K
L
F
S
K
Narcissus serotinus
K
Y
Y
H
R
S
S
Y
K
F
L
S
K
Narcissus tazetta
K
Y
Y
H
R
S
S
Y
K
F
L
S
K
Narcissus triandrus
R
D
H
H
L
S
A
C
K
L
L
S
Q
Amino acid at each position number
Species
13
34
47
75
78
93
101
108
112
131
142
152
162
Galanthus nivalis (Common snowdrop) =
outgroup
K
Y
Y
H
R
Y
S
Y
K
L
L
S
K
Narcissus serotinus
K
Y
Y
H
R
S
S
Y
K
F
L
S
K
Narcissus tazetta
K
Y
Y
H
R
S
S
Y
K
F
L
S
K
Narcissus calcicola
K
Y
Y
H
R
S
S
C
K
L
F
S
K
Narcissus atlanticus
K
Y
Y
R
R
S
S
C
K
L
F
S
K
Narcissus scaberulus
K
Y
Y
R
R
S
S
C
K
L
F
S
K
Narcissus longispathus
K
Y
Y
H
R
S
A
C
Q
L
L
S
Q
Narcissus nevadensis
K
Y
Y
H
R
S
A
C
Q
L
L
S
Q
Narcissus cernuus
R
D
H
H
L
S
A
C
K
L
L
S
Q
Narcissus triandrus
R
D
H
H
L
S
A
C
K
L
L
S
Q
Narcissus pseudonarcissus
R
Y
H
H
R
S
A
C
K
L
L
N
Q
Narcissus jacetanus
R
Y
H
H
R
P
A
C
K
L
L
N
Q
Narcissus asturiensis
R
Y
H
H
R
P
A
C
K
L
L
N
Q
There are many equally correct ways of organising the table but for the
next step to work all of the green blocks in any column need to be next
to each other.
Amino acid at each position number
Species
13
34
47
75
78
93
101
108
112
131
142
152
162
Galanthus nivalis (Common snowdrop) =
outgroup
K
Y
Y
H
R
Y
S
Y
K
L
L
S
K
Narcissus serotinus
K
Y
Y
H
R
S
S
Y
K
F
L
S
K
Narcissus tazetta
K
Y
Y
H
R
S
S
Y
K
F
L
S
K
Narcissus calcicola
K
Y
Y
H
R
S
S
C
K
L
F
S
K
Narcissus atlanticus
K
Y
Y
R
R
S
S
C
K
L
F
S
K
Narcissus scaberulus
K
Y
Y
R
R
S
S
C
K
L
F
S
K
Narcissus longispathus
K
Y
Y
H
R
S
A
C
Q
L
L
S
Q
Narcissus nevadensis
K
Y
Y
H
R
S
A
C
Q
L
L
S
Q
Narcissus cernuus
R
D
H
H
L
S
A
C
K
L
L
S
Q
Narcissus triandrus
R
D
H
H
L
S
A
C
K
L
L
S
Q
Narcissus pseudonarcissus
R
Y
H
H
R
S
A
C
K
L
L
N
Q
Narcissus jacetanus
R
Y
H
H
R
P
A
C
K
L
L
N
Q
Narcissus asturiensis
R
Y
H
H
R
P
A
C
K
L
L
N
Q
This is quite a complicated tree. Remember that evolutionary
relationships don’t alter if nodes are rotated so the same tree can
actually look very different if several of the nodes are rotated.
131 L→F
93 Y→S
75 H→R
112 K→Q
108 Y→C
101 S→A
162 K→Q
34 Y→D
78 R→L
142 L→F
13 K→R
47 Y→H
N. jacetanus
N. asturiensis
N. pseudonarcissus
N. triandrus
N. cernuus
N. longispathus
N. nevadensis
N. scaberulus
N. atlanticus
N. calcicola
N. tazetta
N. serotus
G. nivalis
Sheet 5
93 S→P
152 S→N
Choosing species to investigate
Narcissus tazetta
Narcissus triandrus
Narcissus pseudonarcissus
Narcissus jacetanus
Choosing species to investigate
i) Which species is most closely related to the species
that has the lowest known IC50 value? Maybe this one
will have an even lower IC50 value.
Narcissus jacetanus has the lowest IC50 value.
From your evolutionary tree or from the one on sheet 5 you
should be able to see that Narcissus asturiensis is
most closely related to N. jacetanus.
Choosing species to investigate
ii) Which species is most closely related to the species
that has the highest known IC50 value? This is
probably the species least likely to possess a useful
new drug.
Narcissus triandrus has the highest IC50 value.
From your evolutionary tree or from the one on sheet 5 you
should be able to see that Narcissus cernuus is most
closely related to N. triandrus.
Choosing species to investigate
iii) Are there any groups of species on the evolutionary
tree that haven’t been studied at all? Maybe there are
very different chemicals in some of these groups that
might have a much lower IC50 value than any that have
been discovered before. Select 3 species that you
think would be best to study first if we are aiming to
make sure that we have investigated all groups of
species.
There are 3 groups of closely related species that haven’t
been studied (see next slide) and you should have
chosen one from each of them.
131 L→F
93 Y→S
75 H→R
112 K→Q
34 Y→D
78 R→L
N. jacetanus
N. asturiensis
N. pseudonarcissus
N. triandrus
N. cernuus
N. longispathus
N. nevadensis
N. scaberulus
N. atlanticus
N. calcicola
N. tazetta
N. serotus
G. nivalis
Sheet 5
93 S→P
152 S→N
142 L→F
13 K→R
47 Y→H
101 S→A
162 K→Q
108 Y→C
You should have selected
one species from each of
the blue blocks
Choosing species to investigate
iv) Use your evolutionary tree to identify the species
most closely related to the one from the research
article. Maybe this species also has chemicals that will
help in the fight against bird flu.
Narcissus tazetta is the species from the research article.
From your evolutionary tree or from the one on sheet 5 you
should be able to see that Narcissus serotus is most
closely related to N. tazetta.
Summary
You should have:
• Identified reasons why understanding evolutionary
relationships is important.
• Investigated numbers of possible trees.
• Used amino acid sequences to work out the most likely
evolutionary tree for 3 species of Narcissus.
• Identified which types of characteristic are useful for
determining the most likely evolutionary tree.
• Identified these characteristics in amino acid sequences of 12
different species of Narcissus.
• Used this information to construct the most likely evolutionary
tree for these 12 species.
• Used your evolutionary tree and information from research
articles to suggest which species to investigate for new drugs.