wagner chapter 2

Book club

Andreas Wagner,The Origins of Evolutionary Innovations

Chapter 2

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

Metabolic networks,definitions (1)

Genotype: the set of reactions that an organism can catalyze

It also represents the metabolic network of an organism

Represented as a binary string

[1]: A. Wagner, The Origins of Evolutionary Innovations. Figure 2.1

Each genotype is a metabolic network

Matias Rodrigues, J.F. & Wagner, A., 2009. Evolutionary plasticity and innovations in complex metabolic reaction networks. PLoS computational biology, 5(12), p.e1000613.

Example of Genotype space

Each genotype is represented as a binary string

00....00 10....00 110000 111000

00.....1 10....10 ….. …..

00....10 10..110 ….. …..

00..1..0 ….. ….. …..

00.1...0 ….. ….. …..

….. ….. ….. …..


Microbial genotype space

In KEGG, there are about 5800 possible metabolic reactions [1] for microbes

There are 2^5800 possible genotypes

The metabolism of E.coli corresponds to a point in this space (example: the blue cell)

00......0 10....00 110000 111000

00......1 10....10 ….. …..

00....10 10..110 ….. …..

00..1..0 ….. ….. …..

00.1...0 ….. ….. 111110

….. 0...1....1 ….. 111111

….. ….. ….. …..

….. ….. ….. …..

….. ….. ….. …..

….. ….. 0.1.1..0 …..

….. ….. ….. …..

….. ….. ….. …..

….. ….. ….. …..

….. ….. ….. ….. [1]: Matias Rodrigues, J.F. & Wagner, A., 2009. Evolutionary plasticity and innovations in complex metabolic reaction networks. PLoS computational biology, 5(12), p.e1000613.

Distribution of Genetic Distance among microbes

On average, two different microbes share only 33% of reactions

Microbes living in the same habitat can be very different

Wagner, A., 2009. Evolutionary constraints permeate large metabolic networks. BMC evolutionary biology, 9, p.231. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2753571&tool=pmcentrez&rendertype=abstract

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2753571&tool=pmcentrez&rendertype=abstract

Metabolic networks,definitions (2)

Phenotype: whether that organism can survive on a certain sugar as the sole carbon source (...)


Two metabolic genotype networks

Yellow can →survive on Glucose as sole carbon source

Blue can survive →on Alanine as sole carbon source

Green →intersection

0....0 ….. ….. ….. ….. …..

0....1 ….. ….. ….. ….. …..

0...10 ….. ….. ….. ….. …..

0..1.0 ….. ….. …..

0.1..0 ….. ….. …..

0..... ….. ….. …..

….. ….. …..

….. ….. …..

….. ….. …..

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Flux Balance Analysis (FBA)

Flux Balance Analysis is a computational technique It allows to predict whether an organism will

survive on a certain sugar as the sole carbon source (….)

Definitions, overview


In this context, a genotype network is a network of metabolic networks

Exploring a Genotype Network

Let's start from the genotype of E.coli (blue)

We can simulate single gene additions/deletions and predict their effects using Flux Balance Analysis

Each change must preserve the ability to survive on glucose as sole source of carbon

1000 simulations, 10,000 mutations each

00......0 10....00 110000 111000

00......1 10....10 ….. …..

00....10 10..110 ….. …..

00..1..0 ….. ….. …..

00.1...0 ….. ….. 111110

….. 0...1....1 ….. 111111

….. ….. ….. …..

….. ….. ….. …..

….. ….. ….. …..

….. ….. 0.1.1..0 …..

….. ….. ….. …..

….. ….. ….. …..

….. ….. ….. …..

….. ….. ….. …..

Exploring a Genotype Network

alternative representation

[1]: Matias Rodrigues, J.F. & Wagner, A., 2009. Evolutionary plasticity and innovations in complex metabolic reaction networks. PLoS computational biology, 5(12), p.e1000613.

Exploring glucosegenotype network

After 1000 simulations of 10,000 mutations of a genotype network, average distance is 0,76

→ so, a metabolism can change up to 76% of its reactions, and still preserve the ability to survive on glucose


Most neighbors have similar phenotype

E.coli can catalyze ~726 reactions

Genotype space: 5870 reactions

226 reactions are essential to preserve ability of using glucose

Only 3,6% (226/5870) of E.coli metabolome's neighbors can not survive on glucose only [1]

00......0 10....00 110000 111000

00......1 10....10 ….. …..

00....10 10..110 ….. …..

00..1..0 ….. ….. …..

00.1...0 ….. ….. 111110

….. 0...1....1 ….. 111111

….. ….. ….. …..

….. ….. ….. …..

….. ….. ….. …..

….. ….. 0.1.1..0 …..

….. ….. ….. …..

….. ….. ….. …..

….. ….. ….. …..

….. ….. ….. ….. [1]: Matias Rodrigues, J.F. & Wagner, A., 2009. Evolutionary plasticity and innovations in complex metabolic reaction networks. PLoS computational biology, 5(12), p.e1000613.

Neighbors of genotypes in a genotype network

Two genotypes of a genotype network have, by definition, the same phenotype.

But what about their neighbors?


Neighbors of genotypes in a genotype network (1)

Neighbors of two points of a genotype network can be very different

(based on 1000 simulations)


Neighbors of genotypes in a genotype network (2)

Difference between neighbors increases with distance (number of mutations)


Take Home Messages

A metabolism can change a lot, while still preserving the phenotype

Metabolic networks are robust to changes, it is difficult to break its functionality

Definitions, overview


wagner chapter 2

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