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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
Main algorithm. a) Determination of neighbors for each enzyme. b) Determination of minimal path length (MPL). The algorithm is a bread-first search for the shortest distance between all pairs of enzymes. MAX_MPL is the maximum MPL under investigation.
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Figure 11: Main algorithm. a) Determination of neighbors for each enzyme. b) Determination of minimal path length (MPL). The algorithm is a bread-first search for the shortest distance between all pairs of enzymes. MAX_MPL is the maximum MPL under investigation.

Mentions: A set of programs were constructed for determination of the minimal path lengths (MPLs) for all enzyme pairs in the network graph. For each E. coli enzyme the neighboring enzymes were determined (Figure 11a). The main program is a breadth-first search implementation which determines all possible MPLs between all pairs of enzymes (Figure 11b). The general idea for the algorithm is the same as described in Jeong et al [26]. It should be noted that because the graph representing the metabolic network of E. coli is directed there may not be paths between all enzyme pairs in one graph component. All the scripts used in this study were written in Python.


Network analysis of metabolic enzyme evolution in Escherichia coli.

Light S, Kraulis P - BMC Bioinformatics (2004)

Main algorithm. a) Determination of neighbors for each enzyme. b) Determination of minimal path length (MPL). The algorithm is a bread-first search for the shortest distance between all pairs of enzymes. MAX_MPL is the maximum MPL under investigation.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 11: Main algorithm. a) Determination of neighbors for each enzyme. b) Determination of minimal path length (MPL). The algorithm is a bread-first search for the shortest distance between all pairs of enzymes. MAX_MPL is the maximum MPL under investigation.
Mentions: A set of programs were constructed for determination of the minimal path lengths (MPLs) for all enzyme pairs in the network graph. For each E. coli enzyme the neighboring enzymes were determined (Figure 11a). The main program is a breadth-first search implementation which determines all possible MPLs between all pairs of enzymes (Figure 11b). The general idea for the algorithm is the same as described in Jeong et al [26]. It should be noted that because the graph representing the metabolic network of E. coli is directed there may not be paths between all enzyme pairs in one graph component. All the scripts used in this study were written in Python.

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