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The role of cost in yeast gene expression

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Information about The role of cost in yeast gene expression

Published on June 3, 2008

Author: mciahelbarton

Source: slideshare.net

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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

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