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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.

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Homology vs minimal path length (MPL) without the 20 most promiscuous compounds. The plot shows the correlation between homology and MPL when the 20 most promiscuous compounds (Table 2) have been removed. The solid line represents the metabolic network of E. coli.The dotted vertical lines represent three standard deviations of the number of homologous enzyme pairs for the randomized networks. The number of homologous enzyme pairs has been normalized by the average number of homologous enzyme pairs for the randomized networks.
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Figure 7: Homology vs minimal path length (MPL) without the 20 most promiscuous compounds. The plot shows the correlation between homology and MPL when the 20 most promiscuous compounds (Table 2) have been removed. The solid line represents the metabolic network of E. coli.The dotted vertical lines represent three standard deviations of the number of homologous enzyme pairs for the randomized networks. The number of homologous enzyme pairs has been normalized by the average number of homologous enzyme pairs for the randomized networks.

Mentions: The network includes promiscuous compounds such as H2O, ATP and NAD. There are therefore homologous enzyme pairs containing for instance NAD-binding domains that are at MPL 1 because their gene products catalyze reactions involving that cofactor. It could be argued that such coenzyme binding domains give rise to skewed results in our analysis. To remedy this complication we removed 20 compounds, starting from the most promiscuous compound (H2O) down to the 20th most promiscuous compound (O2). We find that the correlation between MPL and homology is preserved (Figure 7), indicating that the abundance of homologous enzyme pairs at MPL 1 is not the result of common cofactor-binding domains alone. We could also detect a marginally significant correlation between MPL and homology at MPL 2 when the 20 most promiscuous compounds had been excluded from the network (Figure 7). No correlation could be detected at MPLs greater than 2. These results were robust for variations in the number of compounds that were removed from the network, i.e. removing between 17 and 23 of the most promiscuous compounds generated the same result (data not shown).


Network analysis of metabolic enzyme evolution in Escherichia coli.

Light S, Kraulis P - BMC Bioinformatics (2004)

Homology vs minimal path length (MPL) without the 20 most promiscuous compounds. The plot shows the correlation between homology and MPL when the 20 most promiscuous compounds (Table 2) have been removed. The solid line represents the metabolic network of E. coli.The dotted vertical lines represent three standard deviations of the number of homologous enzyme pairs for the randomized networks. The number of homologous enzyme pairs has been normalized by the average number of homologous enzyme pairs for the randomized networks.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC394313&req=5

Figure 7: Homology vs minimal path length (MPL) without the 20 most promiscuous compounds. The plot shows the correlation between homology and MPL when the 20 most promiscuous compounds (Table 2) have been removed. The solid line represents the metabolic network of E. coli.The dotted vertical lines represent three standard deviations of the number of homologous enzyme pairs for the randomized networks. The number of homologous enzyme pairs has been normalized by the average number of homologous enzyme pairs for the randomized networks.
Mentions: The network includes promiscuous compounds such as H2O, ATP and NAD. There are therefore homologous enzyme pairs containing for instance NAD-binding domains that are at MPL 1 because their gene products catalyze reactions involving that cofactor. It could be argued that such coenzyme binding domains give rise to skewed results in our analysis. To remedy this complication we removed 20 compounds, starting from the most promiscuous compound (H2O) down to the 20th most promiscuous compound (O2). We find that the correlation between MPL and homology is preserved (Figure 7), indicating that the abundance of homologous enzyme pairs at MPL 1 is not the result of common cofactor-binding domains alone. We could also detect a marginally significant correlation between MPL and homology at MPL 2 when the 20 most promiscuous compounds had been excluded from the network (Figure 7). No correlation could be detected at MPLs greater than 2. These results were robust for variations in the number of compounds that were removed from the network, i.e. removing between 17 and 23 of the most promiscuous compounds generated the same result (data not shown).

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