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Energetic costsin yeast
Michael BartonUniversity ofManchester
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
gly, ser,cys
leu,val
pro, glu,gln, arg
met, asp, asn, thr,
ile
his, tyr,phe, trp
ala,lys
amino acid biosynthetic cost via glycolysis and
TCA cycle
Craig and WeberMol Biol Evol (1998)15:774–776
tryptophan• biosynthetically
expensive• long branch• higher in
glycolysis
serine• biosynthetically
cheap• short branch• further into
glycolysis
What price does thecell have to pay?
What price does thecell have to pay?
e.g. what is the
energy investment
in proteins?
cost vs benefit
£100 million42 goals
£80 million
16 goals
cost decreases with predicted expression level
Akashi & GojoboriPNAS (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
growthGlu
NH4
supply demanddistribution of
resources
Duarte, Herrgård, and PalssonGenome Research (2004) 14:1298–1309
increasing amino acid demand
nutr
ient
sup
ply
increasing amino acid demand
nutr
ient
sup
ply
steeper slope
=
greater cost
trp arg gly
glucose limited cost
trp arg gly
nitrogen limited cost
cost selection • minimise cost• transcript levels• protein levels• amino acid levels
energetic costatomic contentcodon adaptation (CAI)tRNA count
regression
expression level
regression
expression level
energetic costatomic contentcodon adaptation (CAI)tRNA count
cost independent
of codon adaptation
cost carbon nitrogen sulphur tRNA CAI
transcript level
impo
rtan
ce
cost carbon nitrogen sulphur tRNA CAI
transcript level
impo
rtan
ce
translatabilityover costminimisation
cost carbon nitrogen sulphur tRNA CAI
protein level
impo
rtan
ce
cost carbon nitrogen sulphur tRNA CAI
protein level
impo
rtan
ce
translatability
again
cost carbon nitrogen sulphur tRNA
amino acid levels
impo
rtan
ce
variation explained (R2)
amino acids 78%
proteins 41%
transcripts 39%
biosynthetic cost and genome evolution
summary
biosynthetic cost and genome evolution
summary
estimate usingsystems biology
biosynthetic cost and genome evolution
summary
estimate usingsystems biology
cost related trends in
gene expression
acknowledgements• Casey Bergman• Magnus Rattray• Balazs Papp• Daniela Delneri• Steve Oliver
• Ian Donaldson• Raquel Linheiro• Paul Cartwright
more information• preprint tinyurl.com/6c6xdb
• website www.michaelbarton.me.uk
