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Book club
Andreas Wagner,The Origins of Evolutionary Innovations
Chapter 4
Book club presented by G. M. Dall'Olio, Pompeu Fabra, IBE-CEXS
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
Genotype Networksbetter representation!
The Genotype Space can be represented as a Hamming Graph
https://bitbucket.org/dalloliogm/genotype_space
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
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
A genotype space of sequences
A genotype space of sequences (simplified)
O = any Hydrophobic aminoacid Y = any Hydrophilic aminoacid
Novel Moleculesdefinitions (2)
Phenotype: The fold of a protein sequence The secondary structure of a RNA molecule
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
A Genotype network
In this example, all orange sequences have the same fold:
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
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
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.xGoodman 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.
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: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2994758&tool=pmcentrez&rendertype=abstract
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: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2994758&tool=pmcentrez&rendertype=abstract
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)
RNA structures
RNA secondary structures can be predicted in silico
http://rna.ucsc.edu/rnacenter/ribosome_images.html
RNA structure videogame
There is even a videogame on predicting RNA structure:
http://eterna.cmu.edu/
So, predicting RNA structures is (relatively) easy
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
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: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2562401&tool=pmcentrez&rendertype=abstract
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
RNA sequences can withstand 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
RNA sequences can withstand a lot of changes, without modifying the fold
Different sequence, same fold:
http://eterna.cmu.edu/
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
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
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
Phenotype of neighbors of genotype network
Neighbor of genotypes can have very different phenotypes
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: http://www.ncbi.nlm.nih.gov/pubmed/10903205
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
A Genotype network
All blue sequences have the same fold