Limits...
Network analysis of metabolic enzyme evolution in Escherichia coli.

Light S, Kraulis P - BMC Bioinformatics (2004)

Bottom Line: In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model.However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs.Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: Stockholm Bioinformatics Center, Department of Biochemistry and Biophysics, Stockholm Center for Physics, Astronomy and Biotechnology, Stockholm University, Stockholm SE-10691, Sweden. sara@sbc.su.se

ABSTRACT

Background: The two most common models for the evolution of metabolism are the patchwork evolution model, where enzymes are thought to diverge from broad to narrow substrate specificity, and the retrograde evolution model, according to which enzymes evolve in response to substrate depletion. Analysis of the distribution of homologous enzyme pairs in the metabolic network can shed light on the respective importance of the two models. We here investigate the evolution of the metabolism in E. coli viewed as a single network using EcoCyc.

Results: Sequence comparison between all enzyme pairs was performed and the minimal path length (MPL) between all enzyme pairs was determined. We find a strong over-representation of homologous enzymes at MPL 1. We show that the functionally similar and functionally undetermined enzyme pairs are responsible for most of the over-representation of homologous enzyme pairs at MPL 1.

Conclusions: The retrograde evolution model predicts that homologous enzymes pairs are at short metabolic distances from each other. In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model. However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs. Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution.

Show MeSH
Common representation of the biotin metabolism. In the most common representation of biochemical reactions the reactants represent the vertices of the network and the enzymes represent the edges. The drawing of the biotin metabolism was redrawn from EcoCyc [19].
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC394313&req=5

Figure 1: Common representation of the biotin metabolism. In the most common representation of biochemical reactions the reactants represent the vertices of the network and the enzymes represent the edges. The drawing of the biotin metabolism was redrawn from EcoCyc [19].

Mentions: The vertices of the graph we use represent the enzymes catalyzing the reactions. One edge represents one or more compounds. There will be an edge leading from an enzyme E1 to an enzyme E2 if E1 catalyzes a reaction where compound A is produced and E2 takes A as a substrate. Reversible reactions, such as A B, are separated into two reactions, A → B and B → A. There can be at most one edge in each direction between a pair of enzymes. Note that the representation used herein is different from the common representation of metabolic pathways where the substrates and products are the vertices and the enzymes catalyzing the reactions are the edges (Figure 1). The type of network representation used in our study has been used before for metabolic network analysis where it has been referred to as 'protein-centric' graphs [23] and 'reaction graphs' [24] (Figure 2).


Network analysis of metabolic enzyme evolution in Escherichia coli.

Light S, Kraulis P - BMC Bioinformatics (2004)

Common representation of the biotin metabolism. In the most common representation of biochemical reactions the reactants represent the vertices of the network and the enzymes represent the edges. The drawing of the biotin metabolism was redrawn from EcoCyc [19].
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC394313&req=5

Figure 1: Common representation of the biotin metabolism. In the most common representation of biochemical reactions the reactants represent the vertices of the network and the enzymes represent the edges. The drawing of the biotin metabolism was redrawn from EcoCyc [19].
Mentions: The vertices of the graph we use represent the enzymes catalyzing the reactions. One edge represents one or more compounds. There will be an edge leading from an enzyme E1 to an enzyme E2 if E1 catalyzes a reaction where compound A is produced and E2 takes A as a substrate. Reversible reactions, such as A B, are separated into two reactions, A → B and B → A. There can be at most one edge in each direction between a pair of enzymes. Note that the representation used herein is different from the common representation of metabolic pathways where the substrates and products are the vertices and the enzymes catalyzing the reactions are the edges (Figure 1). The type of network representation used in our study has been used before for metabolic network analysis where it has been referred to as 'protein-centric' graphs [23] and 'reaction graphs' [24] (Figure 2).

Bottom Line: In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model.However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs.Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: Stockholm Bioinformatics Center, Department of Biochemistry and Biophysics, Stockholm Center for Physics, Astronomy and Biotechnology, Stockholm University, Stockholm SE-10691, Sweden. sara@sbc.su.se

ABSTRACT

Background: The two most common models for the evolution of metabolism are the patchwork evolution model, where enzymes are thought to diverge from broad to narrow substrate specificity, and the retrograde evolution model, according to which enzymes evolve in response to substrate depletion. Analysis of the distribution of homologous enzyme pairs in the metabolic network can shed light on the respective importance of the two models. We here investigate the evolution of the metabolism in E. coli viewed as a single network using EcoCyc.

Results: Sequence comparison between all enzyme pairs was performed and the minimal path length (MPL) between all enzyme pairs was determined. We find a strong over-representation of homologous enzymes at MPL 1. We show that the functionally similar and functionally undetermined enzyme pairs are responsible for most of the over-representation of homologous enzyme pairs at MPL 1.

Conclusions: The retrograde evolution model predicts that homologous enzymes pairs are at short metabolic distances from each other. In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model. However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs. Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution.

Show MeSH