Evolutionary relationships and finding new drugs in daffodils

1
Evolutionary relationshipsandfinding 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.
2
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.
3
Why constructing phylogenies (or understanding
evolutionary relationships) is important
4
How phylogenies are constructed
5
An example of a phlogenetic tree
Gorillas
Humans
Chimpanzees
6
How many possible trees for 3 species?
7
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
8
How many possible trees for 4 species?
9
How many possible trees for 4 species?
D C A B
D B A C
So there are 12 of one shape and 3 of another
making 15 possible trees overall for 4 species
D A B C
C D A B
C B A D
C A B D
B D A C
B C A D
B A C D
A D B C
A D B C
A C B D
A C B D
A B C D
A B C D
10
Choosing the most likely evolutionary tree
1. Identifying evolutionary change in Amino acids
11
1. Galanthus nivalis (Common snowdrop) 2.
Narcissus cernuus 3. Narcissus tazetta 4.
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 VK 2b. AKDSSDWCEF
LKNAVFSVSI ALFGLFVASI LYGSVYSSLQ NLGLVNSFVK
KSPKRILLDQ AQ 3b. SKDSSDWYEF LKNAVFSVSI
ALFGLFVASI FYGSVYSSLQ NLGLVNSFVK KSPKRILLDQ
VK 4b. AKDSSDWCEF LKNAVFSVSI ALFGLFVASI
LYGSVYSSLQ NLGLVNSFVK KNPKRILLDQ VQ
12
Choosing the most likely evolutionary tree
2. Mapping characters onto possible evolutionary
trees
13
B
A
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.
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.
C
14
Identifying the informative characteristics
15
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
16
Creating a useful phylogeny
17
Species Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number 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
18
Species Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number 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
19
Species Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number 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.
20
Species Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number Amino acid at each position number 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 dont alter if nodes
are rotated so the same tree can actually look
very different if several of the nodes are
rotated.
21
Sheet 5
N. pseudonarcissus
N. longispathus
N. asturiensis
N. scaberulus
N. nevadensis
N. jacetanus
N. serotus
N. tazetta
N. calcicola
N. atlanticus
N. cernuus
N. triandrus
G. nivalis
22
Choosing species to investigate
23
Narcissus tazetta
Narcissus triandrus
Narcissus pseudonarcissus
Narcissus jacetanus
24
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.

25
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.

26
Choosing species to investigate

• iii) Are there any groups of species on the
  evolutionary tree that havent 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 havent been studied (see next slide) and
  you should have chosen one from each of them.

27
Sheet 5
N. pseudonarcissus
N. longispathus
N. asturiensis
N. scaberulus
N. nevadensis
N. jacetanus
N. serotus
N. tazetta
N. calcicola
N. atlanticus
N. cernuus
N. triandrus
G. nivalis
You should have selected one species from each of
the blue blocks
28
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.

29
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.