1. Energ
etic c
in yea osts
st
Micha
el Bar
ton
Unive
rsity o
Manc f
heste
r

2. cost of a new cell
• protein
• fats
• nucleic acids
• ...

3. cost selection hypothesis
• cost of synthesis reflected in genome
• evolve to minimise cost
• selection prefers a bargain?

4. energy is currency?
• ATP
• NADPH

5. Craig and Weber
his, tyr, Mol Biol Evol (1998)15:774–776
phe, trp
amino acid
gly, ser, biosynthetic cost
cys
via glycolysis and
ala,
lys
TCA cycle
leu,
met, asp, val
asn, thr,
ile
pro, glu,
gln, arg

6. tryptophan
• biosynthetically
expensive
• long branch
• higher in
glycolysis

7. serine
• biosynthetically
cheap
• short branch
• further into
glycolysis

8. What price does the
cell have to pay?

9. What price does the
cell have to pay?
at i s the
e. g. wh ent
inv estm
en ergy ins?
in p rote

10. £10
0m
42 illio
goa n
ls
cost vs benefit
il lion
0 m als
£8 go
16

11. cost decreases with
predicted expression level
Akashi & Gojobori
PNAS (2002) 99:3695–3700

12. but, is there a
single currency?

13. systems biology approach

14. yeast genome scale model
• 750 metabolic reactions
• can predict growth on different media
• can predict mutant phenotypes

15. inputs

16. outputs

17. Duarte, Herrgård, and Palsson
Genome Research (2004) 14:1298–1309
NH4
growth
Glu
supply distribution of
demand
resources

18. nutrient supply
increasing amino acid demand

19. nutrient supply
per s lope
stee
=
eater cost
gr
increasing amino acid demand

20. trp arg gly
glucose limited cost

21. trp arg gly
nitrogen limited cost

22. cost selection
• minimise cost
• transcript levels
• protein levels
• amino acid levels

23. regression
energetic cost
atomic content
expression level
codon adaptation (CAI)
tRNA count

24. regression
energetic cost
atomic content
expression level
codon adaptation (CAI)
tRNA count
depen dent
c ost in apta tion
o f cod on ad

25. importance
cost carbon nitrogen sulphur tRNA CAI
transcript level

26. trans
latab
ility
importance
over c
mini ost
misa
tion
cost carbon nitrogen sulphur tRNA CAI
transcript level

27. importance
cost carbon nitrogen sulphur tRNA CAI
protein level

28. ility
importance
nsl atab
tra
ag ain
cost carbon nitrogen sulphur tRNA CAI
protein level

29. importance
cost carbon nitrogen sulphur tRNA
amino acid levels

30. transcripts 39%
proteins 41%
amino acids 78%
variation explained (R2)

31. summary
biosynthetic cost and genome evolution

32. summary
biosynthetic cost and genome evolution
estimate u
sing
systems bi
ology

33. summary
biosynthetic cost and genome evolution
estimate u
sing ated trends in
systems bi cost rel
ology ene expression
g

34. acknowledgements
• Casey Bergman • Ian Donaldson
• Magnus Rattray • Raquel Linheiro
• Balazs Papp • Paul Cartwright
• Daniela Delneri
• Steve Oliver

35. more information
• preprint tinyurl.com/6c6xdb
• website www.michaelbarton.me.uk