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Wagner chapter 4


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Book club on "Origins of Evolutionary Innovations" by A. Wagner

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Wagner chapter 4

  1. 1. Book club Andreas Wagner,The Origins of Evolutionary Innovations Chapter 4Book 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. Genotype Networks better representation! The Genotype Space can be represented as a Hamming Graph
  4. 4. Chapter 4: Novel Molecules This chapter describes the relationship between  protein/RNA sequence and tertiary structure Most RNA/Proteins have the same fold but  different sequences
  5. 5. Novel Molecules, definitions (1) Genotype:   def 1: the aminoacid sequence of a protein  (or the list of hydrophobic)  def 2: the nucleotidic sequence of a RNA 
  6. 6. A genotype space of sequences
  7. 7. A genotype space of sequences (simplified) O = any Hydrophobic aminoacid Y = any Hydrophilic aminoacid
  8. 8. Novel Molecules definitions (2) Phenotype:   The fold of a protein sequence  The secondary structure of a RNA molecule
  9. 9. Protein Structures It is also possible to  predict the fold of a  protein But it is difficult, so  here we focus on  “lattice models” In a lattice model, we  only use hydrophobic  or hydrophilic  aminoacids
  10. 10. A Genotype network In this example, all orange sequences have the same fold:
  11. 11. More sequences than folds Li et al, 1996: study on lattice protein models:  There are many more protein sequences than folds  Some phenotypes are formed by more sequences  than others  Sequences that produce the same fold can be very  different Rost, 1997: study on 272 proteins with similar  folds. They shared 8.5% of aa seq
  12. 12. There are many more protein sequences than protein folds Globins are a very common protein domain Most globins have different sequence, but the same  fold Among some hemoglobins, only 12.4% of aa  residues are identical
  13. 13. Do globins have a common origin? Bailly, X., Chabasse, C., Hourdez, S., Dewilde, S., Martial, S., Moens, L. and Zal, F. (2007), Globin gene family evolution and functional diversification in annelids. FEBS Journal, 274: 2641–2652. doi: 10.1111/j.1742- 4658.2007.05799.x Goodman M, Pedwaydon J, Czelusniak J, Suzuki T, Gotoh T, Moens L, Shishikura F, Walz D, Vinogradov S. An evolutionary tree for invertebrate globin sequences. J Mol Evol. 1988;27(3):236-49. PubMed PMID: 3138426.
  14. 14. Some folds are more common than others Some folds can be obtained by an higher number of  sequences than others Number of proteins Sequences by structure (Ferrada,  Wagner 2010):  Ferrada, E. & Wagner, A., 2010. Evolutionary innovations and the organization of protein functions in genotype space. PloS one, 5(11), p.e14172. Available at:
  15. 15. The 10 most structurally promiscuous functions Promiscuity of a function: when the function can be  obtained by different structures/sequences Ferrada, E. & Wagner, A., 2010. Evolutionary innovations and the organization of protein functions in genotype space. PloS one, 5(11), p.e14172. Available at:
  16. 16. Genotype networks of protein sequences Sequences that have  the same fold tend to  be connected in a  genotype network  (from Li et al, 1996) More the case of figure  1 (above) than figure  2 (below)
  17. 17. RNA structures RNA secondary structures can be predicted in silico
  18. 18. RNA structure videogame There is even a  videogame on  predicting RNA  structure:  So, predicting RNA  structures is  (relatively) easy
  19. 19. Innovations in RNA folds All the observations made for protein sequences are  also valid for RNA, in a bigger scale:  On average, 400 million RNA seqs per fold  Very long RNA sequences tend to similar folds
  20. 20. There are many more RNA sequences than RNA folds Size rank of genotype set by frequency Wagner, A., 2008. Robustness and evolvability: a paradox resolved. Proceedings. Biological sciences / The Royal Society, 275(1630), pp.91-100. Available at:
  21. 21. Frequent RNA structures def. frequent RNA structure: a RNA structure that  can be obtained by > 5000 sequences Only 10% of RNA structures are frequent 93% of RNA sequences belong to frequent RNA  structures
  22. 22. RNA sequences canwithstand a lot of changes,without modifying the fold Maximal genotype distance in a RNA gen. network: A. Wagner, The Origins of Evolutionary Innovations. Figure 4.6
  23. 23. RNA sequences canwithstand a lot of changes,without modifying the fold Different sequence, same fold:
  24. 24. Neighbors of points in the genotype network Most neighbors of sequences in the space have the  same fold A. Wagner, The Origins of Evolutionary Innovations. Figure 4.7
  25. 25. Neighbors of points in the genotype network Most neighbors of sequences in the space have the same  fold This means that the genotype network of a RNA fold is  usually dense RNA genotype network is more likely to fig 1 than fig 2:Fig 1 Fig 2
  26. 26. Neighbors of genotypes in a genotype network Two sequences on a  genotype network  have, by definition,  the same fold. But what about their  neighbors? A. Wagner, The Origins of Evolutionary Innovations. Figure 2.6
  27. 27. Phenotype of neighbors of genotype network Neighbor of genotypes  can have very  different phenotypes
  28. 28. Novel RNA phenotypes Schultes and Bartel:  designed a new  rybozime from two  existing ones Existing enzymes had  <25% sequence  similarity and no  common structure Few mutations needed  to obtain the hybrid Schultes, E. a & Bartel, D.P., 2000. One sequence, two ribozymes: implications for the emergence of new ribozyme folds. Science (New York, N.Y.), 289(5478), pp.448-52. Available at:
  29. 29. Take Home messages There are many more sequences than protein/RNA  folds Some folds correspond to more sequences than  others Sequences that produce the same fold can be very  different New folds can be reached by changing few bases
  30. 30. A Genotype network All blue sequences have the same fold