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

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

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

energy is currency?
• ATP
• NADPH

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

tryptophan
• biosynthetically
expensive
• long branch
• higher in
glycolysis

serine
• biosynthetically
cheap
• short branch
• further into
glycolysis

What price does the
cell have to pay?

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

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

but, is there a
single currency?

systems biology approach

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

inputs

outputs

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

nutrient supply
increasing amino acid demand

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

trp arg gly
glucose limited cost

trp arg gly
nitrogen limited cost

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

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

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

importance
cost carbon nitrogen sulphur tRNA CAI
transcript level

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

importance
cost carbon nitrogen sulphur tRNA CAI
protein level

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

importance
cost carbon nitrogen sulphur tRNA
amino acid levels

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

summary
biosynthetic cost and genome evolution

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

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

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

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