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Evolutionary relationshipsand
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 drugsa) 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?
A B C
B A C
C A B
So there are 3 possible trees for 3 species
How many possible trees for 3 species?
How many possible trees for 4 species?
How many possible trees for 4 species?
A B C D A C B D A D B C B A C D B C A D B D A C C A B D C B A D C D A B D A B C D B A C D C A B
A B C D A C B D A D B C
So there are 12 of one shape and 3 of another making 15 possible trees overall for 4 species
Choosing the most likely evolutionary tree
1. Identifying evolutionary change in Amino acids
1. Galanthus nivalis (Common snowdrop)2. Narcissus cernuus3. Narcissus tazetta4. Narcissus asturiensis
1a. INRNLLLSTM NNKVSFFSKD IYRIDDNVRN RVRYFSTYFR NKYTCTYPHE SDNTMLFPLL VLGLFTLFIG AIGIHFDRGV IDFDLLSKWI TPYADFFHPN 2a. VNRNLLLSTM NNRVSFFSKD IYRIDDNVRN GVRDFSTYFR NKYTYTHPHE SDNTMLFPLL VLVLFPLFIG AIGIHFDLGV IDFDLLSKWL TPSADFFHPN 3a. VNRNLLLSTM NNKVSFFSKD IYRIDDNVRN GVRYFSTYFR NKYTYTYPHE SDNTMLFPLL VLVLFTLFIG AIGIHFDRGV IDFDLLSKWL TPSADFFHPN 4a. VNRNLLLSTM NNRVSFFSKD IYRIDDNVRN GVRYFSTYFR NKYTYTHPHE SDNTMLFPLL VLVLFTLFIG AIGIHFDRGV IDFDLLSKWL TPPADFFHPN
1b. SKDSSDWYEF LKNVVFSVSI ALFGLFVASI LYGSVYSSLQ NLGLVNSFVK KSPKRILLDQ VK2b. AKDSSDWCEF LKNAVFSVSI ALFGLFVASI LYGSVYSSLQ NLGLVNSFVK KSPKRILLDQ AQ3b. SKDSSDWYEF LKNAVFSVSI ALFGLFVASI FYGSVYSSLQ NLGLVNSFVK KSPKRILLDQ VK4b. AKDSSDWCEF LKNAVFSVSI ALFGLFVASI LYGSVYSSLQ NLGLVNSFVK KNPKRILLDQ VQ
Choosing the most likely evolutionary tree
2. Mapping characters onto possible evolutionary trees
Nar
ciss
us c
ernu
us
Nar
ciss
us a
stur
iens
is
Nar
ciss
us ta
zetta
Gal
anth
us n
ival
is
93 Y→S
93 S→P
Nar
ciss
us c
ernu
us
Nar
ciss
us a
stur
iens
is
Nar
ciss
us ta
zetta
Gal
anth
us n
ival
is
93 Y→S
93 S→P
Gal
anth
us n
ival
is
Nar
ciss
us c
ernu
us
Nar
ciss
us ta
zetta
Nar
ciss
us a
stur
iens
is
93 Y→S
93 S→P
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.
A B
C
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.
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.
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 areshared, derived characteristics
Identifying the informative characteristics
Creating a useful phylogeny
Species
Amino acid at each position number
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
Species
Amino acid at each position number
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
Species
Amino acid at each position number
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.
Species
Amino acid at each position number
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.
G.
niv
ali
s
N.
se
rotu
s
N.
taze
tta
N.
ca
lcic
ola
N.
atl
an
tic
us
N.
sc
ab
eru
lus
N.
ne
va
de
ns
is
N.
lon
gis
pa
thu
s
N.
ce
rnu
us
N.
tria
nd
rus
N.
ps
eu
do
na
rcis
su
s
N.
as
turi
en
sis
N.
jac
eta
nu
s
93 Y→S
131 L→F 75 H→R
142 L→F
108 Y→C
101 S→A
162 K→Q
112 K→Q34 Y→D
78 R→L
13 K→R
47 Y→H
152 S→N
93 S→P
Sheet 5
Choosing species to investigate
Narcissus tazetta
Narcissus pseudonarcissus Narcissus jacetanus
Narcissus triandrus
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 investigateiii) 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.
G.
niv
ali
s
N.
se
rotu
s
N.
taze
tta
N.
ca
lcic
ola
N.
atl
an
tic
us
N.
sc
ab
eru
lus
N.
ne
va
de
ns
is
N.
lon
gis
pa
thu
s
N.
ce
rnu
us
N.
tria
nd
rus
N.
ps
eu
do
na
rcis
su
s
N.
as
turi
en
sis
N.
jac
eta
nu
s
93 Y→S
131 L→F 75 H→R
142 L→F
108 Y→C
101 S→A
162 K→Q
112 K→Q34 Y→D
78 R→L
13 K→R
47 Y→H
152 S→N
93 S→P
Sheet 5
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.
SummaryYou 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.