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The role of cost in yeast gene expression

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The role of cost in yeast gene expression

  1. 1. Energ etic c in yea osts st Micha el Bar ton Unive rsity o Manc f heste r
  2. 2. cost of a new cell • protein • fats • nucleic acids • ...
  3. 3. cost selection hypothesis • cost of synthesis reflected in genome • evolve to minimise cost • selection prefers a bargain?
  4. 4. energy is currency? • ATP • NADPH
  5. 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. 6. tryptophan • biosynthetically expensive • long branch • higher in glycolysis
  7. 7. serine • biosynthetically cheap • short branch • further into glycolysis
  8. 8. What price does the cell have to pay?
  9. 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. £10 0m 42 illio goa n ls cost vs benefit il lion 0 m als £8 go 16
  11. 11. cost decreases with predicted expression level Akashi & Gojobori PNAS (2002) 99:3695–3700
  12. 12. but, is there a single currency?
  13. 13. systems biology approach
  14. 14. yeast genome scale model • 750 metabolic reactions • can predict growth on different media • can predict mutant phenotypes
  15. 15. inputs
  16. 16. outputs
  17. 17. Duarte, Herrgård, and Palsson Genome Research (2004) 14:1298–1309 NH4 growth Glu supply distribution of demand resources
  18. 18. nutrient supply increasing amino acid demand
  19. 19. nutrient supply per s lope stee = eater cost gr increasing amino acid demand
  20. 20. trp arg gly glucose limited cost
  21. 21. trp arg gly nitrogen limited cost
  22. 22. cost selection • minimise cost • transcript levels • protein levels • amino acid levels
  23. 23. regression energetic cost atomic content expression level codon adaptation (CAI) tRNA count
  24. 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. 25. importance cost carbon nitrogen sulphur tRNA CAI transcript level
  26. 26. trans latab ility importance over c mini ost misa tion cost carbon nitrogen sulphur tRNA CAI transcript level
  27. 27. importance cost carbon nitrogen sulphur tRNA CAI protein level
  28. 28. ility importance nsl atab tra ag ain cost carbon nitrogen sulphur tRNA CAI protein level
  29. 29. importance cost carbon nitrogen sulphur tRNA amino acid levels
  30. 30. transcripts 39% proteins 41% amino acids 78% variation explained (R2)
  31. 31. summary biosynthetic cost and genome evolution
  32. 32. summary biosynthetic cost and genome evolution estimate u sing systems bi ology
  33. 33. summary biosynthetic cost and genome evolution estimate u sing ated trends in systems bi cost rel ology ene expression g
  34. 34. acknowledgements • Casey Bergman • Ian Donaldson • Magnus Rattray • Raquel Linheiro • Balazs Papp • Paul Cartwright • Daniela Delneri • Steve Oliver
  35. 35. more information • preprint tinyurl.com/6c6xdb • website www.michaelbarton.me.uk

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