Book club          Andreas Wagner,The Origins of Evolutionary Innovations              Chapter 3Book club presented by G. ...
Reminder:               Genotype network   A genotype network is a set of genotypes that have the same       phenotype, a...
Chapter 3:     Regulatory Innovations   This chapter describes the evolution of regulation      mediated by Transcription...
Regulatory innovations,         definitions (1)   Genotype: a square      matrix, called      “Gene regulatory      Circu...
Understanding Gene                Circuits   Gene 1 (first column):          activates Gene 2 and              Gene 5 (o...
Genotype Space of             Regulatory Circuits     Each cell corresponds to a regulatory circuit matrix 00000      010...
Neighbors of Regulatory           Circuits   Each circuit differs for one reaction                                Ciliber...
Regulatory innovations,         definitions (2)   Et is the list of expression status of each gene at a       time t:    ...
Genotype Networks in          Regulatory networks     Yellow cells have the same phenotype:               E∞ = (Egene1(t...
Dimensions of Genotype          networks   Genotype networks of regulatory circuits can be      very big   An organism c...
Galactose metabolism in     Yeast and C.albicans   In Yeast, GAL4       initiates the       transcription of        enzym...
Regulation of mating in      Yeast and C.albicans   In yeast, the Cph1 homologue is involved in mating       type determi...
Galactose metabolism in     Yeast and C.albicans   The regulatory network for galactose metabolism      has changed dramm...
Galactose metabolism in         fungii         Figure from: Rokas A, & Hittinger CT (2007). Transcriptional rewiring: the ...
Evolvability of Gene          NetworksAuthors introduced 600 new regulatory interactions  in E.coli, and it tolerated 95% ...
Example: Stem Cells          transformation   Changes of very few transcription factors can      transform a cell into a ...
Robustness to change is a requisite for innovations              Ciliberti, S., Martin, O.C. & Wagner, a, 2007. Innovation...
The number of phenotypes   is much smaller than the number of genotypes   Number of genotypes: 3^(S^2), where S=number of...
Some phenotypes havemore genotypes than others                [1]: A. Wagner, The Origins of Evolutionary Innovations. Fig...
Distance between circuits    with the same phenotype   On average, two      circuits from the      same genotype      net...
Phenotypes of neighbors   Neighbors of two      genotypes in the      same network are      usually different            ...
Distance between two       genotype networks   On average, all the      genotype networks      are interwoven    The dis...
Take Home messages   Genotype networks of regulatory      circuits are large   Regulatory phenotypes are robust      to ...
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Wagner chapter 3

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Wagner chapter 3

  1. 1. Book club Andreas Wagner,The Origins of Evolutionary Innovations Chapter 3Book club presented by G. M. DallOlio, Pompeu Fabra, IBE-CEXS
  2. 2. Reminder: Genotype network A genotype network is a set of genotypes that have the same  phenotype, and are connected by single pairwise differences AAAAA AAAAC AAAAG AAAAT AAATT AAACA AAACC AAACG AAACT AAATC AACCA AACCC AACCG AACCT ….. ACCCA ACCCC ACCCG ACCCT ….. CCCCA CCCCC CCCCG CCCCT ….. ….. ….. ….. ….. ….. Yellow = same phenotype = a genotype network Note: genotype network == neutral network
  3. 3. Chapter 3: Regulatory Innovations This chapter describes the evolution of regulation  mediated by Transcription Factors binding sites Regulation is much more difficult to study than  metabolic networks
  4. 4. Regulatory innovations, definitions (1) Genotype: a square  matrix, called  “Gene regulatory  Circuit” Describes the  interactions  between regulation  factors Ciliberti, S., Martin, O.C. & Wagner, a, 2007. Innovation and robustness in complex regulatory gene networks.PNAS, 104(34), pp.13591-6. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1959426
  5. 5. Understanding Gene Circuits Gene 1 (first column):  activates Gene 2 and  Gene 5 (orange)  inhibits Gene 4  (blue) Ciliberti, S., Martin, O.C. & Wagner, a, 2007. Innovation and robustness in complex regulatory gene networks.PNAS, 104(34), pp.13591-6. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1959426 (image adapter for color blind people)
  6. 6. Genotype Space of Regulatory Circuits  Each cell corresponds to a regulatory circuit matrix 00000 01000 01000 01000 0100000000 00000 00100 00100 0010000000 00000 00000 00010 0001000000 00000 00000 00000 0000100000 00000 00000 00000 0000010000 11000 11000 11000 1100000000 00000 00100 00100 0010000000 00000 00000 00010 0001000000 00000 00000 00000 0000100000 00000 00000 00000 0000010000 11000 11000 11000 1100001000 01000 01100 01100 0110000000 00000 00000 00010 0001000000 00000 00000 00000 0000100000 00000 00000 00000 00000
  7. 7. Neighbors of Regulatory Circuits Each circuit differs for one reaction Ciliberti, S., Martin, O.C. & Wagner, a, 2007. Innovation and robustness in complex regulatory gene networks.PNAS, 104(34), pp.13591-6. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1959426 (image adapter for color blind people)
  8. 8. Regulatory innovations, definitions (2) Et is the list of expression status of each gene at a  time t:  Et = (Egene1(t), Egene2(t), Egene3(t), Egene4(t), Egene5(t)) Phenotype: the expression state E∞ at equilibrium
  9. 9. Genotype Networks in Regulatory networks  Yellow cells have the same phenotype:  E∞ = (Egene1(t=∞), Egene2(t=∞), Egene3(t=∞), Egene4(t=∞), Egene5(t=∞))  We can make some observations without knowing the identity of the genes.00000 01000 01000 01000 0100000000 00000 00100 00100 0010000000 00000 00000 00010 0001000000 00000 00000 00000 0000100000 00000 00000 00000 0000010000 11000 11000 11000 1100000000 00000 00100 00100 0010000000 00000 00000 00010 0001000000 00000 00000 00000 0000100000 00000 00000 00000 0000010000 11000 11000 11000 1100001000 01000 01100 01100 0110000000 00000 00000 00010 0001000000 00000 00000 00000 0000100000 00000 00000 00000 00000
  10. 10. Dimensions of Genotype networks Genotype networks of regulatory circuits can be  very big An organism can stand many changes to its  regulatory network, without changing the  phenotype
  11. 11. Galactose metabolism in Yeast and C.albicans In Yeast, GAL4  initiates the  transcription of   enzymes required for  galactose metabolism In C.albicans, GAL4 is  associated to  telomere and has  unknown function Traven A, Jelicic B, Sopta M. Yeast Gal4: a transcriptional paradigm revisited. EMBO Rep. 2006 May;7(5):496-9. Review. PubMed PMID: 16670683; PubMed Central PMCID: PMC1479557
  12. 12. Regulation of mating in Yeast and C.albicans In yeast, the Cph1 homologue is involved in mating  type determination (...) In C.albicans, Cph1 is involved in galactose  metabolism
  13. 13. Galactose metabolism in Yeast and C.albicans The regulatory network for galactose metabolism  has changed drammatically from S.cerevisiae to  C.albicans Figure from: Rokas A, & Hittinger CT (2007). Transcriptional rewiring: the proof is in the eating. Current biology : CB, 17 (16) PMID: 17714646 See also: Martchenko, M., Levitin, A., Hogues, H., Nantel, A., & Whiteway, M. (2007). Transcriptional Rewiring of Fungal Galactose-Metabolism Circuitry Current Biology, 17 (12), 1007-1013 DOI: 10.1016/j.cub.2007.05.017
  14. 14. Galactose metabolism in fungii Figure from: Rokas A, & Hittinger CT (2007). Transcriptional rewiring: the proof is in the eating. Current biology : CB, 17 (16) PMID: 17714646 See also: Martchenko, M., Levitin, A., Hogues, H., Nantel, A., & Whiteway, M. (2007). Transcriptional Rewiring of Fungal Galactose-Metabolism Circuitry Current Biology, 17 (12), 1007-1013 DOI: 10.1016/j.cub.2007.05.017
  15. 15. Evolvability of Gene NetworksAuthors introduced 600 new regulatory interactions  in E.coli, and it tolerated 95% of them Isalan M, Lemerle C, Michalodimitrakis K, Horn C, Beltrao P, Raineri E, Garriga-Canut M, Serrano L. Evolvability and hierarchy in rewired bacterial gene networks. Nature. 2008 Apr 17;452(7189):840-5. PubMed PMID: 18421347; PubMed Central PMCID: PMC2666274.
  16. 16. Example: Stem Cells transformation Changes of very few transcription factors can  transform a cell into a stem cell, or another type Graf T, Enver T. Forcing cells to change lineages. Nature. 2009 Dec 3;462(7273):587-94. Review. PubMed PMID: 19956253.
  17. 17. Robustness to change is a requisite for innovations Ciliberti, S., Martin, O.C. & Wagner, a, 2007. Innovation and robustness in complex regulatory gene networks.PNAS, 104(34), pp.13591-6. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1959426
  18. 18. The number of phenotypes is much smaller than the number of genotypes Number of genotypes: 3^(S^2), where S=number of  genes Number of phenotypes: 2^(2*S) There are much more genotypes than phenotypes
  19. 19. Some phenotypes havemore genotypes than others [1]: A. Wagner, The Origins of Evolutionary Innovations. Figure 3.2 Ciliberti, S., Martin, O.C. & Wagner, a, 2007. Innovation and robustness in complex regulatory gene networks.PNAS, 104(34), pp.13591-6. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1959426
  20. 20. Distance between circuits with the same phenotype On average, two  circuits from the  same genotype  network differ by  about 80% of their  reactions Ciliberti, S., Martin, O.C. & Wagner, a, 2007. Innovation and robustness in complex regulatory gene networks.PNAS, 104(34), pp.13591-6. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1959426
  21. 21. Phenotypes of neighbors Neighbors of two  genotypes in the  same network are  usually different [1]: A. Wagner, The Origins of Evolutionary Innovations. Figure 3.6 [1]: A. Wagner, The Origins of Evolutionary  Innovations. Figure 2.6
  22. 22. Distance between two genotype networks On average, all the  genotype networks  are interwoven  The distance to pass  from a phenotype to  another is usually  shorter than the  distance between two  circuits in the same  network Ciliberti, S., Martin, O.C. & Wagner, a, 2007. Innovation and robustness in complex regulatory gene networks.PNAS, 104(34), pp.13591-6. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1959426
  23. 23. Take Home messages Genotype networks of regulatory  circuits are large Regulatory phenotypes are robust  to changes (e.g. GAT4 in  S.cerevisiae/C.albicans) Many more genotypes than  phenotypes Ciliberti, S., Martin, O.C. & Wagner, a, 2007. Innovation and robustness in complex regulatory gene networks.PNAS, 104(34), pp.13591-6. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1959426

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